Publications by authors named "Arno A W Roest"

97 Publications

Pulmonary ductal coarctation: An entity associated with congenital heart defects involving the right ventricle outflow tract.

J Card Surg 2021 Oct 12. Epub 2021 Oct 12.

Division of Pediatric Cardiology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

We present a case of a prematurely born 2-month-old girl with a double outlet right ventricle with pulmonary atresia and a left pulmonary artery coarctation arising after ductal closure. The case highlights the importance of knowledge and identification of such an anomaly in patients with congenital heart malformations with severe pulmonary stenosis to atresia.
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http://dx.doi.org/10.1111/jocs.16067DOI Listing
October 2021

The Influence of Respiration on Blood Flow in the Fontan Circulation: Insights for Imaging-Based Clinical Evaluation of the Total Cavopulmonary Connection.

Front Cardiovasc Med 2021 5;8:683849. Epub 2021 Aug 5.

Department of Cardiology, Biomedical Engineering, Biomechanics Laboratory, Rotterdam, Netherlands.

Congenital heart disease is the most common birth defect and functionally univentricular heart defects represent the most severe end of this spectrum. The Fontan circulation provides an unique solution for single ventricle patients, by connecting both caval veins directly to the pulmonary arteries. As a result, the pulmonary circulation in Fontan palliated patients is characterized by a passive, low-energy circulation that depends on increased systemic venous pressure to drive blood toward the lungs. The absence of a subpulmonary ventricle led to the widely believed concept that respiration, by sucking blood to the pulmonary circulation during inspiration, is of great importance as a driving force for antegrade blood flow in Fontan patients. However, recent studies show that respiration influences pulsatility, but has a limited effect on net forward flow in the Fontan circulation. Importantly, since MRI examination is recommended every 2 years in Fontan patients, clinicians should be aware that most conventional MRI flow sequences do not capture the pulsatility of the blood flow as a result of the respiration. In this review, the unique flow dynamics influenced by the cardiac and respiratory cycle at multiple locations within the Fontan circulation is discussed. The impact of (not) incorporating respiration in different MRI flow sequences on the interpretation of clinical flow parameters will be covered. Finally, the influence of incorporating respiration in advanced computational fluid dynamic modeling will be outlined.
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http://dx.doi.org/10.3389/fcvm.2021.683849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374887PMC
August 2021

Hemodynamic Consequences of an Undersized Extracardiac Conduit in an Adult Fontan Patient Revealed by 4-Dimensional Flow Magnetic Resonance Imaging.

Circ Cardiovasc Imaging 2021 Aug 12;14(8):e012612. Epub 2021 Aug 12.

Radiology (H.C.v.A., J.J.M.W.), Leiden University Medical Center, the Netherlands.

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http://dx.doi.org/10.1161/CIRCIMAGING.121.012612DOI Listing
August 2021

Ductal Flow Ratio as Measure of Transition in Preterm Infants After Birth: A Pilot Study.

Front Pediatr 2021 19;9:668744. Epub 2021 Jul 19.

Division of Paediatric Cardiology, Department of Paediatrics, Leiden University Medical Centre, Leiden, Netherlands.

Cardiovascular changes during the transition from intra- to extrauterine life, alters the pressure gradient across the ductus arteriosus (DA). DA flow ratio (R-L/L-R) has been suggested to reflect the infant's transitional status and could potentially predict neonatal outcomes after preterm birth. Determine whether DA flow ratio correlates with oxygenation parameters in preterm infants at 1 h after birth. Echocardiography was performed in preterm infants born <32 weeks gestational age (GA), as part of an ancillary study. DA flow was measured at 1 h after birth. DA flow ratio was correlated with FiO, SpO, and SpO/FiO (SF) ratio. The DA flow ratio of infants receiving physiological-based cord clamping (PBCC) or time-based cord clamping (TBCC) were compared. Measurements from 16 infants were analysed (median [IQR] GA 29 [27-30] weeks; birthweight 1,176 [951-1,409] grams). R-L DA shunting was 16 [17-27] ml/kg/min and L-R was 110 [81-124] ml/kg/min. The DA flow ratio was 0.18 [0.11-0.28], SpO 94 [93-96]%, FiO was 23 [21-28]% and SF ratio 4.1 [3.3-4.5]. There was a moderate correlation between DA flow ratio and SpO [correlation coefficient (CC) -0.415; = 0.110], FiO (CC 0.384; = 0.142) and SF ratio (CC -0.356; = 0.175). There were no differences in DA flow measurements between infants where PBBC or TBCC was performed. In this pilot study we observed a non-significant positive correlation between DA flow ratio at 1 h after birth and oxygenation parameters in preterm infants.
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http://dx.doi.org/10.3389/fped.2021.668744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326397PMC
July 2021

Imaging of Congenital Heart Disease: Expect the Unexpected.

Radiology 2021 07 20;300(1):174-175. Epub 2021 Apr 20.

From the Department of Pediatrics, Division of Pediatric Cardiology J6-S (A.A.W.R.), and Department of Radiology (H.J.L.), Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands.

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http://dx.doi.org/10.1148/radiol.2021210285DOI Listing
July 2021

Non-uniform mixing of hepatic venous flow and inferior vena cava flow in the Fontan conduit.

J R Soc Interface 2021 04 7;18(177):20201027. Epub 2021 Apr 7.

Department of Pediatric Cardiology, Leiden University Medical Center, Leiden, The Netherlands.

Fontan patients require a balanced hepatic blood flow distribution (HFD) to prevent pulmonary arteriovenous malformations. Currently, HFD is quantified by tracking Fontan conduit flow, assuming hepatic venous (HV) flow to be uniformly distributed within the Fontan conduit. However, this assumption may be unvalid leading to inaccuracies in HFD quantification with potential clinical impact. The aim of this study was to (i) assess the mixing of HV flow and inferior vena caval (IVC) flow within the Fontan conduit and (ii) quantify HFD by directly tracking HV flow and quantitatively comparing results with the conventional approach. Patient-specific, time-resolved computational fluid dynamic models of 15 total cavopulmonary connections were generated, including the HV and subhepatic IVC. Mixing of HV and IVC flow, on a scale between 0 (no mixing) and 1 (perfect mixing), was assessed at the caudal and cranial Fontan conduit. HFD was quantified by tracking particles from the caudal (HFD) and cranial (HFD) conduit and from the hepatic veins (HFD). HV flow was non-uniformly distributed at both the caudal (mean mixing 0.66 ± 0.13) and cranial (mean 0.79 ± 0.11) level within the Fontan conduit. On a cohort level, differences in HFD between methods were significant but small; HFD (51.0 ± 20.6%) versus HFD (48.2 ± 21.9%, = 0.033) or HFD (48.0 ± 21.9%, = 0.044). However, individual absolute differences of 8.2-14.9% in HFD were observed in 4/15 patients. HV flow is non-uniformly distributed within the Fontan conduit. Substantial individual inaccuracies in HFD quantification were observed in a subset of patients with potential clinical impact.
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http://dx.doi.org/10.1098/rsif.2020.1027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086942PMC
April 2021

Reduced scan time and superior image quality with 3D flow MRI compared to 4D flow MRI for hemodynamic evaluation of the Fontan pathway.

Sci Rep 2021 03 22;11(1):6507. Epub 2021 Mar 22.

Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.

Long scan times prohibit a widespread clinical applicability of 4D flow MRI in Fontan patients. As pulsatility in the Fontan pathway is minimal during the cardiac cycle, acquiring non-ECG gated 3D flow MRI may result in a reduction of scan time while accurately obtaining time-averaged clinical parameters in comparison with 2D and 4D flow MRI. Thirty-two Fontan patients prospectively underwent 2D (reference), 3D and 4D flow MRI of the Fontan pathway. Multiple clinical parameters were assessed from time-averaged flow rates, including the right-to-left pulmonary flow distribution (main endpoint) and systemic-to-pulmonary collateral flow (SPCF). A ten-fold reduction in scan time was achieved [4D flow 15.9 min (SD 2.7 min) and 3D flow 1.6 min (SD 7.8 s), p < 0.001] with a superior signal-to-noise ratio [mean ratio of SNRs 1.7 (0.8), p < 0.001] and vessel sharpness [mean ratio 1.2 (0.4), p = 0.01] with 3D flow. Compared to 2D flow, good-excellent agreement was shown for mean flow rates (ICC 0.82-0.96) and right-to-left pulmonary flow distribution (ICC 0.97). SPCF derived from 3D flow showed good agreement with that from 4D flow (ICC 0.86). 3D flow MRI allows for obtaining time-averaged flow rates and derived clinical parameters in the Fontan pathway with good-excellent agreement with 2D and 4D flow, but with a tenfold reduction in scan time and significantly improved image quality compared to 4D flow.
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http://dx.doi.org/10.1038/s41598-021-85936-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985309PMC
March 2021

Hemodynamic interplay of vorticity, viscous energy loss, and kinetic energy from 4D Flow MRI and link to cardiac function in healthy subjects and Fontan patients.

Am J Physiol Heart Circ Physiol 2021 04 26;320(4):H1687-H1698. Epub 2021 Feb 26.

Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

The purpose of this study was to directly assess (patho)physiology of intraventricular hemodynamic interplay between four-dimensional flow cardiovascular magnetic resonance imaging (4D Flow MRI)-derived vorticity with kinetic energy (KE) and viscous energy loss (EL) over the cardiac cycle and their association to ejection fraction (EF) and stroke volume (SV). Fifteen healthy subjects and thirty Fontan patients underwent whole heart 4D Flow MRI. Ventricular vorticity, KE, and EL were computed over systole (vorticity_vol, KE, and EL) and diastole (vorticity_vol, KE, and EL). The association between vorticity_vol and KE and EL was tested by Spearman correlation. Fontan patients were grouped to normal and impaired EF groups. A significant correlation was found between SV and vorticity in healthy subjects (systolic: ρ = 0.84, < 0.001; diastolic: ρ = 0.81, < 0.001) and in Fontan patients (systolic: ρ = 0.61, < 0.001; diastolic: ρ = 0.54, = 0.002). Healthy subjects showed positive correlation between vorticity_vol versus KE (systole: ρ = 0.96, < 0.001; diastole: ρ = 0.90, < 0.001) and EL (systole: ρ = 0.85, < 0.001; diastole: ρ = 0.84, < 0.001). Fontan patients showed significantly elevated vorticity_vol compared with healthy subjects (vorticity_vol: 3.1 [2.3-3.9] vs. 1.7 [1.3-2.4] L/s, < 0.001; vorticity_vol: 3.1 [2.0-3.7] vs. 2.1 [1.6-2.8] L/s, = 0.002). This elevated vorticity in Fontan patients showed strong association with KE (systole: ρ = 0.91, < 0.001; diastole: ρ = 0.85, < 0.001) and EL (systole: ρ = 0.82, < 0.001; diastole: ρ = 0.89, < 0.001). Fontan patients with normal EF showed significantly higher vorticity_vol and EL, but significantly decreased KE , in the presence of normal SV, compared with healthy subjects. Healthy subjects show strong physiological hemodynamic interplay between vorticity with KE and EL. Fontan patients demonstrate a pathophysiological hemodynamic interplay characterized by correlation of elevated vorticity with KE and EL in the presence of maintained normal stroke volume. Altered vorticity and energetic hemodynamics are found in the presence of normal EF in Fontan patients. Physiologic intraventricular hemodynamic interplay/coupling is present in the healthy left ventricle between vorticity versus viscous energy loss and kinetic energy from four-dimensional flow cardiovascular magnetic resonance imaging (4D Flow MRI). Conversely, Fontan patients present compensatory pathophysiologic hemodynamic coupling by an increase in intraventricular vorticity that positively correlates to viscous energy loss and kinetic energy levels in the presence of maintained normal stroke volume. Altered vorticity and energetics are found in the presence of normal ejection fraction in Fontan patients.
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http://dx.doi.org/10.1152/ajpheart.00806.2020DOI Listing
April 2021

Associations Between Blood Biomarkers, Cardiac Function, and Adverse Outcome in a Young Fontan Cohort.

J Am Heart Assoc 2021 02 24;10(5):e015022. Epub 2021 Feb 24.

Division of Pediatric Cardiology Department of Pediatrics Erasmus University Medical Center Rotterdam The Netherlands.

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 young cohort who have undergone the Fontan procedure. Methods and Results In 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 (=0.005) and vWF (=0.008) and high levels of DLK-1 (=0.041). There was a positive correlation (β=0.33, =0.003) between DLK-1 and stress cardiac magnetic resonance imaging functional reserve. Conclusions NT-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.
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http://dx.doi.org/10.1161/JAHA.119.015022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174257PMC
February 2021

Respiratory distress syndrome and bronchopulmonary dysplasia after fetal growth restriction: Lessons from a natural experiment in identical twins.

EClinicalMedicine 2021 Feb 29;32:100725. Epub 2021 Jan 29.

Neonatology, Dept. of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands.

Background: Fetal growth restriction (FGR) is thought to negatively affect lung development resulting in increased respiratory morbidity. However, research performed in singletons is often limited by a certain level of bias caused by individual differences in genetic constitution, obstetrical and maternal factors.

Methods: Respiratory morbidity was compared between the smaller and the larger twin in monochorionic twins with selective fetal growth restriction (sFGR), defined as a birth weight discordance ≥ 20%, born in our center between 2010 and 2019 in this retrospective study. Respiratory distress syndrome (RDS) was diagnosed based on the clinical picture of a neonate with respiratory failure requiring mechanical ventilation and/or surfactant, confirmed by a chest X-ray. Bronchopulmonary dysplasia (BPD) was diagnosed when the neonate required treatment with >21% oxygen for at least 28 days.

Findings: Median gestational age at birth for the 94 included pregnancies was 32.4 (IQR 30.4-34.3) weeks. Within-pair analyses showed that the prevalence of RDS was lower in the smaller twin compared to the larger twin, 19.1% (18/94) vs 34.0% (32/94), respectively ( = 0.004). The odds of RDS for the larger twin was doubled (OR 2.1 (CI95% 1.3-3.5). In contrast, the rate of BPD in the smaller twin was higher as opposed to the larger twin, 16.7% (15/90) vs 6.7% (6/89), respectively ( = 0.008), with a more than doubled odds (OR 2.5 (CI95% 1.3-4.9)).

Interpretation: Despite being genetically identical, sFGR twins have different respiratory outcomes. Adverse growth condition in the smaller twin is associated with a reduced odds of RDS at birth but a more than doubled odds of BPD, reflecting the pathophysiologic adverse effect of growth restriction on lung development.

Funding: The Dutch Heart Foundation (2017T075).
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http://dx.doi.org/10.1016/j.eclinm.2021.100725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851769PMC
February 2021

Wall shear stress in the thoracic aorta at rest and with dobutamine stress after arterial switch operation.

Eur J Cardiothorac Surg 2021 04;59(4):814-822

Department of Radiology, Leiden University Medical Center, Leiden, Netherlands.

Objectives: Progressive root dilatation is an important complication in patients with transposition of the great arteries (TGA) after arterial switch operation (ASO) that may be caused by altered flow dynamics. Aortic wall shear stress (WSS) distribution at rest and under dobutamine stress (DS) conditions using 4D flow magnetic resonance imaging were investigated in relation to thoracic aorta geometry.

Methods: 4D flow magnetic resonance imaging was performed in 16 adolescent TGA patients after ASO (rest and DS condition) and in 10 healthy controls (rest). The primary outcome measure was the WSS distribution along the aortic segments and the WSS change with DS in TGA patients. Based on the results, we secondary zoomed in on factors [aortic geometry and left ventricular (LV) function parameters] that might relate to these WSS distribution differences. Aortic diameters, arch angle, LV function parameters (stroke volume, LV ejection fraction, cardiac output) and peak systolic aortic WSS were obtained.

Results: TGA patients had significantly larger neoaortic root and smaller mid-ascending aorta (AAo) dimensions and aortic arch angle. At rest, patients had significantly higher WSS in the entire thoracic aorta, except for the dilated root. High WSS levels beyond the proximal AAo were associated with the diameter decrease from the root to the mid-AAo (correlation coefficient r = 0.54-0.59, P = 0.022-0.031), not associated with the aortic arch angle. During DS, WSS increased in all aortic segments (P < 0.001), most pronounced in the AAo segments. The increase in LV ejection fraction, stroke volume and cardiac output as a result of DS showed a moderate linear relationship with the WSS increase in the distal AAo (correlation coefficient r = 0.54-0.57, P = 0.002-0.038).

Conclusions: Increased aortic WSS was observed in TGA patients after ASO, related to the ASO-specific geometry, which increased with DS. Stress-enhanced elevated WSS may play a role in neoaortic root dilatation and anterior aortic wall thinning of the distal AAo.
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http://dx.doi.org/10.1093/ejcts/ezaa392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083947PMC
April 2021

Reproducibility of Aorta Segmentation on 4D Flow MRI in Healthy Volunteers.

J Magn Reson Imaging 2021 04 11;53(4):1268-1279. Epub 2020 Nov 11.

Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.

Background: Hemodynamic aorta parameters can be derived from 4D flow MRI, but this requires lumen segmentation. In both commercially available and research 4D flow MRI software tools, lumen segmentation is mostly (semi-)automatically performed and subsequently manually improved by an observer. Since the segmentation variability, together with 4D flow MRI data and image processing algorithms, will contribute to the reproducibility of patient-specific flow properties, the observer's lumen segmentation reproducibility and repeatability needs to be assessed.

Purpose: To determine the interexamination, interobserver reproducibility, and intraobserver repeatability of aortic lumen segmentation on 4D flow MRI.

Study Type: Prospective and retrospective.

Population: A healthy volunteer cohort of 10 subjects who underwent 4D flow MRI twice. Also, a clinical cohort of six subjects who underwent 4D flow MRI once.

Field Strength/sequence: 3T; time-resolved three-directional and 3D velocity-encoded sequence (4D flow MRI).

Assessment: The thoracic aorta was segmented on the 4D flow MRI in five systolic phases. By positioning six planes perpendicular to a segmentation's centerline, the aorta was divided into five segments. The volume, surface area, centerline length, maximal diameter, and curvature radius were determined for each segment.

Statistical Tests: To assess the reproducibility, the coefficient of variation (COV), Pearson correlation coefficient (r), and intraclass correlation coefficient (ICC) were calculated.

Results: The interexamination and interobserver reproducibility and intraobserver repeatability were comparable for each parameter. For both cohorts there was very good reproducibility and repeatability for volume, surface area, and centerline length (COV = 10-32%, r = 0.54-0.95 and ICC = 0.65-0.99), excellent reproducibility and repeatability for maximal diameter (COV = 3-11%, r = 0.94-0.99, ICC = 0.94-0.99), and good reproducibility and repeatability for curvature radius (COV = 25-62%, r = 0.73-0.95, ICC = 0.84-0.97).

Data Conclusion: This study demonstrated no major reproducibility and repeatability limitations for 4D flow MRI aortic lumen segmentation.

Level Of Evidence: 3 TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984392PMC
April 2021

Ethnic differences in childhood right and left cardiac structure and function assessed by cardiac magnetic resonance imaging.

Eur J Pediatr 2021 Apr 10;180(4):1257-1266. Epub 2020 Nov 10.

The Generation R Study Group (Na 2915), Erasmus MC, University Medical Center, PO Box 2040, 3000 CA, Rotterdam, the Netherlands.

Ethnic differences in cardiovascular risk factors and disease are well-known and may originate in early-life. We examined the ethnic differences in cardiac structure and function in children using cardiac magnetic resonance imaging in a European migrant population, and whether any difference was explained by early life factors. We used a prospective population-based cohort study among 2317 children in Rotterdam, the Netherlands. We compared children from Dutch (73%), Cape Verdean (3.5%), Dutch Antillean (3.3%), Moroccan (6.1%), Surinamese-Creoles (3.9%), Surinamese-Hindustani (3.4%), and Turkish (6.4%) background. Main outcomes were cMRI-measured cardiac structures and function. Cardiac outcomes were standardized on body surface area. Cape Verdean, Surinamese-Hindustani, and Turkish children had smaller right ventricular end-diastolic volume and left ventricular end-diastolic volume relative to their body size than Dutch children (p < 0.05). These results were not fully explained by fetal and childhood factors. Right ventricular ejection fraction and left ventricular ejection fraction did not differ between ethnicities after adjustment for fetal and childhood factors.Conclusion: Right ventricular end-diastolic volume and left ventricular end-diastolic volume differ between ethnic subgroups in childhood, without affecting ejection fraction. Follow-up studies are needed to investigate whether these differences lead to ethnic differences in cardiac disease in adulthood. What is Known: • Ethnic differences in cardiovascular risk factors and disease are well-known and may originate in early-life. • The prevalence of cardiovascular disease differs between ethnic groups. What is New: • We examined ethnic differences in left and right cardiac structure and function in children using cMRI. • Right and left cardiac dimensions differ between ethnic groups in childhood and are only partly explained by fetal and childhood factors.
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http://dx.doi.org/10.1007/s00431-020-03869-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940261PMC
April 2021

The Cardiovascular Stress Response as Early Life Marker of Cardiovascular Health: Applications in Population-Based Pediatric Studies-A Narrative Review.

Pediatr Cardiol 2020 Dec 2;41(8):1739-1755. Epub 2020 Sep 2.

The Generation R Study Group, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.

Stress inducement by physical exercise requires major cardiovascular adaptations in both adults and children to maintain an adequate perfusion of the body. As physical exercise causes a stress situation for the cardiovascular system, cardiovascular exercise stress tests are widely used in clinical practice to reveal subtle cardiovascular pathology in adult and childhood populations with cardiac and cardiovascular diseases. Recently, evidence from small studies suggests that the cardiovascular stress response can also be used within research settings to provide novel insights on subtle differences in cardiovascular health in non-diseased adults and children, as even among healthy populations an abnormal response to physical exercise is associated with an increased risk of cardiovascular diseases. This narrative review is specifically focused on the possibilities of using the cardiovascular stress response to exercise combined with advanced imaging techniques in pediatric population-based studies focused on the early origins of cardiovascular diseases. We discuss the physiology of the cardiovascular stress response to exercise, the type of physical exercise used to induce the cardiovascular stress response in combination with advanced imaging techniques, the obtained measurements with advanced imaging techniques during the cardiovascular exercise stress test and their associations with cardiovascular health outcomes. Finally, we discuss the potential for cardiovascular exercise stress tests to use in pediatric population-based studies focused on the early origins of cardiovascular diseases.
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http://dx.doi.org/10.1007/s00246-020-02436-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695663PMC
December 2020

Associations of Maternal Glycemia in the First Half of Pregnancy With Alterations in Cardiac Structure and Function in Childhood.

Diabetes Care 2020 09 13;43(9):2272-2280. Epub 2020 Jul 13.

Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands

Objective: Gestational diabetes mellitus has been associated with offspring cardiac congenital malformations, ventricular hypertrophy, and diastolic dysfunction in large observational cohort studies and experimental animal models. We assessed the associations of maternal random glucose concentrations across the full range with childhood cardiac ventricular structure and function.

Research Design And Methods: In a population-based prospective cohort among 1,959 women and their offspring, maternal random glucose concentrations were measured at a median 13.1 weeks' gestation (95% range 10.5-16.8 weeks). We obtained offspring cardiac outcomes, relative to body size, through cardiac MRI at 10 years.

Results: The mean maternal random glucose concentration was 4.4 mmol/L (SD 0.8). The highest quintile of maternal glucose concentrations, compared with the lowest quintile, was associated with a lower childhood left ventricular mass (-0.19 SD score [SDS]; 95% CI -0.31, -0.07) and left ventricular end-diastolic volume (-0.17 SDS; 95% -0.28, -0.05). Also, higher maternal glucose concentrations across the full range per 1 mmol/L increase were associated with a lower childhood left ventricular mass and left ventricular end-diastolic volume ( values ≤0.05). Adjustment for maternal prepregnancy BMI, gestational age, and weight at birth or childhood BMI and blood pressure did not influence the effect estimates. Maternal glucose concentrations were not significantly associated with childhood right ventricular end-diastolic volume or left and right ventricular ejection fraction.

Conclusions: Higher maternal random glucose concentrations in the first half of pregnancy are associated with a lower childhood left ventricular mass and left ventricular end-diastolic volume, with the strongest associations for childhood left ventricular mass. These associations were not explained by maternal, birth, or childhood characteristics. Further studies are needed to replicate these findings using repeated maternal glucose measurements throughout pregnancy and offspring cardiac outcomes throughout childhood and adulthood.
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http://dx.doi.org/10.2337/dc19-2580DOI Listing
September 2020

Pulmonary ductal coarctation and left pulmonary artery interruption; pathology and role of neural crest and second heart field during development.

PLoS One 2020 15;15(5):e0228478. Epub 2020 May 15.

Department of Anatomy & Embryology, Leiden University Medical Center, Leiden, The Netherlands.

Objectives: In congenital heart malformations with pulmonary stenosis to atresia an abnormal lateral ductus arteriosus to left pulmonary artery connection can lead to a localised narrowing (pulmonary ductal coarctation) or even interruption We investigated embryonic remodelling and pathogenesis of this area.

Material And Methods: Normal development was studied in WntCre reporter mice (E10.0-12.5) for neural crest cells and Nkx2.5 immunostaining for second heart field cells. Data were compared to stage matched human embryos and a VEGF120/120 mutant mouse strain developing pulmonary atresia.

Results: Normal mouse and human embryos showed that the mid-pharyngeal endothelial plexus, connected side-ways to the 6th pharyngeal arch artery. The ventral segment formed the proximal pulmonary artery. The dorsal segment (future DA) was solely surrounded by neural crest cells. The ventral segment had a dual outer lining with neural crest and second heart field cells, while the distal pulmonary artery was covered by none of these cells. The asymmetric contribution of second heart field to the future pulmonary trunk on the left side of the aortic sac (so-called pulmonary push) was evident. The ventral segment became incorporated into the pulmonary trunk leading to a separate connection of the left and right pulmonary arteries. The VEGF120/120 embryos showed a stunted pulmonary push and a variety of vascular anomalies.

Summary: Side-way connection of the DA to the left pulmonary artery is a congenital anomaly. The primary problem is a stunted development of the pulmonary push leading to pulmonary stenosis/atresia and a subsequent lack of proper incorporation of the ventral segment into the aortic sac. Clinically, the aberrant smooth muscle tissue of the ductus arteriosus should be addressed to prohibit development of severe pulmonary ductal coarctation or even interruption of the left pulmonary artery.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228478PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228067PMC
July 2020

Editorial for "Evaluation of Cardiac Shunts With 4D Flow Cardiac Magnetic Resonance: Intra- and Interobserver Variability".

J Magn Reson Imaging 2020 10 3;52(4):1064-1065. Epub 2020 May 3.

Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.

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http://dx.doi.org/10.1002/jmri.27175DOI Listing
October 2020

Pericardial adipose tissue, cardiac structures, and cardiovascular risk factors in school-age children.

Eur Heart J Cardiovasc Imaging 2021 02;22(3):307-313

Generation R Study Group, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.

Aims: We examined the associations of pericardial adipose tissue with cardiac structures and cardiovascular risk factors in children.

Methods And Results: We performed a cross-sectional analysis in a population-based cohort study among 2892 children aged 10 years (2404 normal weight and 488 overweight/obese). Pericardial adipose tissue mass was estimated by magnetic resonance imaging (MRI) and indexed on height3. Left ventricular mass (LVM) and left ventricular mass-to-volume ratio (LMVR) were estimated by cardiac MRI. Cardiovascular risk factors included android adipose tissue percentage obtained by Dual-energy X-ray absorptiometry, blood pressure and glucose, insulin, cholesterol, and triglycerides concentrations. Adverse outcomes were defined as values above the 75 percentile. Median pericardial adipose tissue index was 3.6 (95% range 1.6-7.1) among normal weight and 4.7 (95% range 2.0-8.9) among overweight children. A one standard deviation (1 SD) higher pericardial adipose tissue index was associated with higher LMVR [0.06 standard deviation scores, 95% confidence interval (CI) 0.02-0.09], increased odds of high android adipose tissue [odd ratio (OR) 2.08, 95% CI 1.89-2.29], high insulin concentrations (OR 1.17, 95% CI 1.06-1.30), an atherogenic lipid profile (OR 1.22, 95% CI 1.11-1.33), and clustering of cardiovascular risk factors (OR 1.56, 95% CI 1.36-1.79). Pericardial adipose tissue index was not associated with LVM, blood pressure, and glucose concentrations. The associations showed largely the same directions but tended to be weaker among normal weight than among overweight children.

Conclusion: Pericardial adipose tissue is associated with cardiac adaptations and cardiovascular risk factors already in childhood in both normal weight and overweight children.
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http://dx.doi.org/10.1093/ehjci/jeaa031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899276PMC
February 2021

Altered Ascending Aorta Hemodynamics in Patients After Arterial Switch Operation for Transposition of the Great Arteries.

J Magn Reson Imaging 2020 04 7;51(4):1105-1116. Epub 2019 Oct 7.

Division of Pediatric Cardiology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

Background: Patients with transposition of the great arteries (TGA) have an altered aortic geometry after an arterial switch operation (ASO), with neo-aortic root dilatation as an important complication. Geometry-related aortic hemodynamics have been assumed to contribute to pathology of the ascending aorta (AAo).

Purpose: To evaluate aortic flow displacement (FD) and regional wall shear stress (WSS) in relation to ascending neo-aortic geometry in children after ASO.

Study Type: Prospective.

Population: Twenty-eight TGA patients after ASO and 10 healthy volunteers.

Field Strength/sequence: 3.0T/4D flow (segmented fast-spoiled echo pulse), noncontrast-enhanced MR angiography (Dixon), and anatomic images (SSFP).

Assessment: Aortic diameters and body surface area-indexed aortic dimensions (Z-scores), normalized FD and planar ascending aortic WSS.

Statistical Tests: Mann-Whitney and chi-square tests for differences in FD magnitude, WSS, and FD directionality between groups, respectively. Spearman rank correlation to assess the degree of association between aortic geometry, FD and WSS parameters. Shapiro-Wilk test to evaluate distribution normality on the absolute differences in octant location between FD and WSS.

Results: TGA patients showed a significantly dilated proximal AAo and relatively small mid-AAo dimensions at the level of the pulmonary arteries (Z-scores neo-aortic root: 4.38 ± 1.96 vs. 1.52 ± 0.70, P < 0.001; sinotubular junction: 3.48 ± 2.67 vs. 1.38 ± 1.30, P = 0.010; mid-AAo: 0.32 ± 3.06 vs. 1.69 ± 1.24, P = 0.001). FD magnitude was higher in TGA patients (neo-aortic root: 0.048 ± 0.027 vs. 0.021 ± 0.006, P < 0.001; sinotubular junction: 0.054 ± 0.037 vs. 0.029 ± 0.013, P < 0.05) and was related to the neo-aortic Z-score. Clear areas of higher WSS at the right and anterior aortic wall regions along the distal AAo were detected in TGA patients, most pronounced in those with relatively smaller mid-AAo diameters.

Data Conclusion: TGA-specific geometry related to the ASO, evidenced by neo-aortic root dilatation and a sudden change in vessel diameter at mid-AAo level, leads to more aortic flow asymmetry in the proximal AAo and WSS distribution with higher WSS at the right and anterior aortic wall regions along the distal AAo.

Level Of Evidence: 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1105-1116.
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http://dx.doi.org/10.1002/jmri.26934DOI Listing
April 2020

Third Trimester Fetal Cardiac Blood Flow and Cardiac Outcomes in School-Age Children Assessed By Magnetic Resonance Imaging.

J Am Heart Assoc 2019 08 13;8(16):e012821. Epub 2019 Aug 13.

Generation R Study Group Erasmus University Medical Center Rotterdam the Netherlands.

Background An adverse fetal environment leads to fetal hemodynamic adaptations with cardiac flow alterations that may subsequently affect cardiac development. We examined the associations of third trimester placental and fetal cardiac hemodynamics with cardiac outcomes in school-age children. Methods and Results We performed a population-based prospective cohort study among 547 mothers and their children. At a gestational age of 30.4 (95% range 28.4-32.7) weeks, we measured umbilical and cerebral artery resistance, cardiac output, and tricuspid and mitral E/A waves with Doppler. At the median age of 10.0 years (95% range 9.4-11.7) we measured cardiac outcomes with cardiac magnetic resonance imaging. Cardiac outcomes included right ventricular end-diastolic volume) and right ventricular ejection fraction, left ventricular end diastolic volume and left ventricular ejection fraction, left ventricular mass, and left ventricular mass-to-volume ratio as left ventricular mass/left ventricular end diastolic volume. Higher third-trimester umbilical artery resistance was associated with higher childhood right ventricular ejection fraction (P value <0.05), but not with other cardiac outcomes. The third-trimester umbilical artery-cerebral artery pulsatility index ratio was not associated with childhood cardiac outcomes. Higher third-trimester fetal left cardiac output was associated with lower childhood left ventricular ejection fraction and higher left ventricular mass-to-volume ratio (P value <0.05). Third-trimester fetal right cardiac output was not associated with childhood cardiac outcomes. A higher third-trimester fetal tricuspid valve E/A ratio was associated with higher childhood right ventricular ejection fraction (P value <0.05). Conclusions Our findings suggest that fetal cardiac fetal blood flow redistribution may have long-term effects on cardiac structure and function. These results should be considered as hypothesis generating and need further replication.
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http://dx.doi.org/10.1161/JAHA.119.012821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759900PMC
August 2019

: The win ongitudinal nvestigation of tal Discordance.

Twin Res Hum Genet 2019 12 25;22(6):617-622. Epub 2019 Jul 25.

Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.

Lifelong health is thought to be partially set during intrauterine life by persistent epigenetic changes induced by the prenatal environment. To evaluate this hypothesis, we initiated a prospective longitudinal study in monochorionic (MC) twins: the TwinLIFE study. MC twins are monozygotic, thus in origin genetically identical, and share a single placenta. Although MC twins have many environmental factors in common, in one-third of the MC twin pairs, one fetus has significantly less access to nutrients and resources during pregnancy than its co-twin often resulting in a significant discordance in prenatal growth. Hence, MC twins constitute a unique natural experiment to study the influence of the prenatal environment on health. In TwinLIFE, we will chart intrapair differences in DNA methylation focusing on mesenchymal stromal cells isolated from cord as an advanced proxy of epigenetic dysregulation relevant for long-term health consequences. Next, we will follow up the MC twins for growth, cardiovascular and neurodevelopmental outcomes during childhood and evaluate the impact of an epigenetic signature at birth on future health. The current target is to include 100 MC twin pairs, but we aim to continue enrollment after procuring additional funding. TwinLIFE will not only address an unmet clinical need in the high-risk group of MC twins, but may also advance early-life strategies to prevent adverse growth, cardiovascular and neurodevelopmental outcomes in the general population.
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http://dx.doi.org/10.1017/thg.2019.38DOI Listing
December 2019

Stress increases intracardiac 4D flow cardiovascular magnetic resonance -derived energetics and vorticity and relates to VOmax in Fontan patients.

J Cardiovasc Magn Reson 2019 07 25;21(1):43. Epub 2019 Jul 25.

Department of Radiology Feinberg School of Medicine, Northwestern University, Chicago, USA.

Background: We hypothesize that dobutamine-induced stress impacts intracardiac hemodynamic parameters and that this may be linked to decreased exercise capacity in Fontan patients. Therefore, the purpose of this study was to assess the effect of pharmacologic stress on intraventricular kinetic energy (KE), viscous energy loss (EL) and vorticity from four-dimensional (4D) Flow cardiovascular magnetic resonance (CMR) imaging in Fontan patients and to study the association between stress response and exercise capacity.

Methods: Ten Fontan patients underwent whole-heart 4D flow CMR before and during 7.5 μg/kg/min dobutamine infusion and cardiopulmonary exercise testing (CPET) on the same day. Average ventricular KE, EL and vorticity were computed over systole, diastole and the total cardiac cycle (vorticity_vol, KE EL). The relation to maximum oxygen uptake (VO max) from CPET was tested by Pearson's correlation or Spearman's rank correlation in case of non-normality of the data.

Results: Dobutamine stress caused a significant 88 ± 52% increase in KE (KE: 1.8 ± 0.5 vs 3.3 ± 0.9 mJ, P < 0.001), a significant 108 ± 49% increase in EL (EL: 0.9 ± 0.4 vs 1.9 ± 0.9 mW, P < 0.001) and a significant 27 ± 19% increase in vorticity (vorticity_vol: 3441 ± 899 vs 4394 ± 1322 mL/s, P = 0.002). All rest-stress differences (%) were negatively correlated to VO max (KE: r = - 0.83, P = 0.003; EL: r = - 0.80, P = 0.006; vorticity_vol: r = - 0.64, P = 0.047).

Conclusions: 4D flow CMR-derived intraventricular kinetic energy, viscous energy loss and vorticity in Fontan patients increase during pharmacologic stress and show a negative correlation with exercise capacity measured by VO max.
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http://dx.doi.org/10.1186/s12968-019-0553-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657113PMC
July 2019

The effects of age at correction of aortic coarctation and recurrent obstruction on adolescent patients: MRI evaluation of wall shear stress and pulse wave velocity.

Eur Radiol Exp 2019 06 20;3(1):24. Epub 2019 Jun 20.

Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.

Background: Coarctation patients before curative reconstruction are exposed to abnormal flow patterns which potentially could cause wall deterioration. This study evaluated the effect of age at correction on the pulse wave velocity (PWV) and peak wall shear stress (WSS) in adolescent patients with corrected coarctation. Effects of valve morphology and presence of reobstruction were also evaluated.

Methods: Twenty-one patients aged 13.7 ± 2.6 years (mean ± standard deviation) were included (bicuspid aortic valve, n = 14; reobstruction, n = 9). Mean age at correction was 1.0 ± 1.8 years. PWV was determined from two high-temporal through-plane phase-contrast magnetic resonance imaging (MRI) acquisitions, for two segments: ascending aorta plus aortic arch and descending aorta. WSS was determined from four-dimensional flow MRI. Peak WSS over five systolic phases was determined for ascending aorta, aortic arch, and descending aorta.

Results: Patients with tricuspid aortic valve showed a significant correlation between the age at correction and descending aorta PWV (r = 0.80, p = 0.010). Significant differences were found between patients without and with reobstruction for peak WSS in the aortic arch (3.9 ± 1.3 Pa versus 6.5 ± 2.2 Pa, respectively; p = 0.003) and descending aorta (5.0 ± 1.3 Pa versus 6.7 ± 1.1 Pa, respectively; p = 0.005).

Conclusions: A prolonged period of abnormal haemodynamic exposure may result in increased aortic wall stiffening. The increased peak WSS as results of a reobstruction possibly promotes different disease progression, which endorse longitudinal follow-up examination of corrected coarctation patients.
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http://dx.doi.org/10.1186/s41747-019-0102-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586735PMC
June 2019

Umbilical Vein Catheter Protruding Through a Pulmonary Vein in a Patient with an Infracardiac Type Total Abnormal Pulmonary Venous Drainage.

Pediatr Cardiol 2019 04 30;40(4):878-879. Epub 2019 Mar 30.

Department of Paediatric Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.

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http://dx.doi.org/10.1007/s00246-019-02094-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451718PMC
April 2019

Tornado-like flow in the Fontan circulation: insights from quantification and visualization of viscous energy loss rate using 4D flow MRI.

Eur Heart J 2019 07;40(26):2170

Department of Pediatric Cardiology, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands.

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http://dx.doi.org/10.1093/eurheartj/ehz160DOI Listing
July 2019

Late effects of pediatric hematopoietic stem cell transplantation on left ventricular function, aortic stiffness and myocardial tissue characteristics.

J Cardiovasc Magn Reson 2019 01 17;21(1). Epub 2019 Jan 17.

Department of Radiology, Leiden University Medical Center, P.O. Box 9600, postal zone C2-S, 2300 RC, Leiden, The Netherlands.

Background: Pediatric hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of cardiovascular disease later in life. As HSCT survival has significantly improved, with a growing number of HSCT indications, tailored screening strategies for HSCT-related late effects are warranted. Little is known regarding the value of cardiovascular magnetic resonance (CMR) for early identification of high-risk patients after HSCT, before symptomatic cardiovascular disease manifests. This study aimed to assess CMR-derived left ventricular (LV) systolic and diastolic function, aortic stiffness and myocardial tissue characteristics in young adults who received HSCT during childhood.

Methods: Sixteen patients (22.1 ± 1.5 years) treated with HSCT during childhood and 16 healthy controls (22.1 ± 1.8 years) underwent 3 T CMR. LV systolic and diastolic function were measured as LV ejection fraction (LVEF), the ratio of transmitral early and late peak filling rate (E/A), the estimated LV filling pressure (E/Ea) and global longitudinal and circumferential systolic strain and diastolic strain rates, using balanced steady-state free precession cine CMR and 2D velocity-encoded CMR over the mitral valve. Aortic stiffness, myocardial fibrosis and steatosis were assessed with 2D velocity-encoded CMR, native T1 mapping and proton CMR spectroscopy (H-CMRS), respectively.

Results: In the patient compared to the control group, E/Ea (9.92 ± 3.42 vs. 7.24 ± 2.29, P = 0.004) was higher, LVEF (54 ± 6% vs. 58 ± 5%, P = 0.055) and global longitudinal strain (GLS) ( -20.7 ± 3.5% vs. -22.9 ± 3.0%, P = 0.063) tended to be lower, while aortic pulse wave velocity (4.40 ± 0.26 vs. 4.29 ± 0.29 m/s, P = 0.29), native T1 (1211 ± 36 vs. 1227 ± 28 ms, P = 0.16) and myocardial triglyceride content (0.47 ± 0.18 vs. 0.50 ± 0.13%, P = 0.202) were comparable. There were no differences between patients and controls in E/A (2.76 ± 0.92 vs. 2.97 ± 0.91, P = 0.60) and diastolic strain rates.

Conclusion: In young adults who received HSCT during childhood, LV diastolic function was decreased (higher estimated LV filling pressure) and LV systolic function (LVEF and GLS) tended to be reduced as compared to healthy controls, whereas no concomitant differences were found in aortic stiffness and myocardial tissue characteristics. When using CMR, assessment of LV diastolic function in particular is important for early detection of patients at risk of HSCT-related cardiovascular disease, which may warrant closer surveillance.
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http://dx.doi.org/10.1186/s12968-018-0513-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335808PMC
January 2019

Inadvertent Migration of Umbilical Venous Catheters Often Leads to Malposition.

Neonatology 2019 15;115(3):205-210. Epub 2019 Jan 15.

Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

Background: Migration of umbilical venous catheters (UVCs) has been described anecdotally.

Objectives: The aim of this paper was to investigate migration of UVCs using ultrasonography (US).

Methods: In a prospective observational study, the position of UVCs was determined using serial US within 24 h, at midweek, and at the end of the week after umbilical catheterization. Migration was recorded in distance and direction. Malposition was defined as a position of the UVC in the heart (right atrium or more distal along the UVC-route), umbilicoportal confluence, or in the umbilical vein. UVC position determined by US was compared with chest X-rays (CXRs) when these were performed for standard care within the same period of 1 h.

Results: Migration of UVCs was detected with US in 25/40 infants (63%) in 32 occasions, leading to malposition in 17/25 (68%) infants. UVCs migrated inwards in 18/32 (56%), leading to a position within the heart in 17/18 occasions. Most migrations occurred before Day 3 (21/32 [66%]). When a CXR was taken at the same time as US was performed (30 occasions), the assessment of the catheter-tip position differed in 23% of the occasions. When malposition was detected by US, this was detected on routinely performed CXRs in 11% of the occasions.

Conclusions: UVCs often migrate following insertion, often leading to malposition. Awareness for this is needed, and US is a feasible alternative for detecting malposition compared to CXRs and avoids additional radiation. Re-evaluation of the position of UVCs at least once, but within 24 h after placement, is recommended.
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http://dx.doi.org/10.1159/000494369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518856PMC
December 2019

Four-dimensional flow magnetic resonance imaging-derived blood flow energetics of the inferior vena cava-to-extracardiac conduit junction in Fontan patients.

Eur J Cardiothorac Surg 2019 Jun;55(6):1202-1210

Department of Pediatric Cardiology, Leiden University Medical Center, Leiden, Netherlands.

Objectives: In patients with the Fontan circulation, systemic venous return flows passively towards the lungs. Because of the absence of the subpulmonary ventricle, favourable blood flow patterns with minimal energy loss are clinically relevant. The region where the inferior vena cava, the hepatic veins and the extracardiac conduit join (IVC-conduit junction) is a potential source of increased energy loss. The aim of this study was to evaluate the relationship between geometry and blood flow patterns in the IVC-conduit junction with associated kinetic energy and energy loss using 4-dimensional flow magnetic resonance imaging (MRI).

Methods: Fourteen extracardiac conduit-Fontan patients underwent 4-dimensional flow MRI. The IVC-conduit junctions were ranked into 3 groups for 3 categories: the geometry, the flow complexity and the conduit mean velocity. The relative increase in the mean velocity from the IVC to the conduit (representing IVC-conduit mismatch) was determined. The peak kinetic energy and mean kinetic energy and energy loss were determined and normalized for volume.

Results: In 4 of 14 patients, adverse geometries led to helical flow patterns and/or acute changes in flow direction. For each category, the most adverse IVC-conduit junctions were associated with an approximate 2.3-3.2-fold and 2.0-2.9-fold increase in kinetic energy and energy loss, respectively. The IVC-conduit mismatch is strongly correlated with the mean kinetic energy and energy loss (r  = 0.80, P  =  0.001 and ρ = 0.83, P <  0.001, respectively) and with body surface area in patients with 16- mm conduits (r  =  0.88, P  =  0.010).

Conclusions: The IVC-conduit junction is a potential source of increased energy loss. Junctions with increased energy loss showed: (i) a distorted geometry leading to adverse blood flow patterns and/or (ii) the IVC-conduit mismatch. Sixteen-millimetre conduits appear to be inadequate for older patients.
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http://dx.doi.org/10.1093/ejcts/ezy426DOI Listing
June 2019

Risk of Clinically Relevant Pericardial Effusion After Pediatric Cardiac Surgery.

Pediatr Cardiol 2019 Mar 11;40(3):585-594. Epub 2018 Dec 11.

Division of Pediatric Cardiology, Department of Pediatrics, Leiden University Medical Center, PO Box 9600, 2300RC, Leiden, The Netherlands.

Pericardial effusion (PE) after pediatric cardiac surgery is common. Because of the lack of a uniform classification of the presence and severity of PE, we evaluated PE altering clinical management: clinically relevant PE. Risk factors for clinically relevant PE were studied. After cardiac surgery, children were followed until 1 month after surgery. Preoperative variables were studied in the complete cohort. Perioperative and postoperative variables were studied in a case-control manner. Patients with and without clinically relevant PE were matched on age, gender, and diagnosis severity in a 1:1 ratio. Multivariate analysis was conducted using important preoperative variables from the complete cohort combined with perioperative and postoperative variables from the case-control data. 1241 surgical episodes in 1031 patients were included. Clinically relevant PE developed in 136 episodes (11.0%). Multivariate correlation with the outcome was present for age, BSA (adjusted odds ratio: 1.6, 95% CI 0.9-2.8), right-sided heart defect (adjusted odds ratio: 1.3, 95% CI 0.9-1.9), history of previous operation (adjusted odds ratio: 0.5, 95% CI 0.3-0.7), cardiopulmonary bypass use (adjusted odds ratio: 2.1, 95% CI 0.9-4.5), duration of CPAP postoperatively, and an inotropic score (adjusted odds ratio: 1.01, 95% CI 0.998-1.03). In this large patient cohort, 11.0% of postoperative periods of pediatric cardiac surgery were complicated by PE requiring alteration of treatment. Secondly, we newly identified cardiopulmonary bypass use and right-sided heart defects as risk factors for clinically relevant PE and confirmed previously described risk factors: age, CPAP duration, BSA, and inotropic score and a previously described risk reductor: history of previous operation.
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http://dx.doi.org/10.1007/s00246-018-2031-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420454PMC
March 2019

Automated Cardiac Valve Tracking for Flow Quantification with Four-dimensional Flow MRI.

Radiology 2019 01 30;290(1):70-78. Epub 2018 Oct 30.

From the Department of Pediatrics, Division of Pediatric Cardiology (V.P.K., A.A.W.R.), Department of Radiology (P.J.v.d.B., L.J.M.K., A.d.R., H.J.L., J.J.M.W.), and Department of Cardiology (N.A.M., J.J.B.), Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands; Netherlands Heart Institute, Utrecht, the Netherlands (V.P.K.); and Pie Medical Imaging BV, Maastricht, the Netherlands (J.P.A.).

Purpose To compare four-dimensional flow MRI with automated valve tracking to manual valve tracking in patients with acquired or congenital heart disease and healthy volunteers. Materials and Methods In this retrospective study, data were collected from 114 patients and 46 volunteers who underwent four-dimensional flow MRI at 1.5 T or 3.0 T from 2006 through 2017. Among the 114 patients, 33 had acquired and 81 had congenital heart disease (median age, 17 years; interquartile range [IQR], 13-49 years), 51 (45%) were women, and 63 (55%) were men. Among the 46 volunteers (median age, 28 years; IQR, 22-36 years), there were 19 (41%) women and 27 (59%) men. Two orthogonal cine views of each valve were used for valve tracking. Wilcoxon signed-rank test was used to compare analysis times, net forward volumes (NFVs), and regurgitant fractions. Intra- and interobserver variability was tested by using intraclass correlation coefficients (ICCs). Results Analysis time was shorter for automated versus manual tracking (all patients, 14 minutes [IQR, 12-15 minutes] vs 25 minutes [IQR, 20-25 minutes]; P < .001). Although overall differences in NFV and regurgitant fraction were comparable between both methods, NFV variation over four valves was smaller for automated versus manual tracking (all patients, 4.9% [IQR, 3.3%-6.7%] vs 9.8% [IQR, 5.1%-14.7%], respectively; P < .001). Regurgitation severity was discordant for seven pulmonary valves, 22 mitral valves, and 21 tricuspid valves. Intra- and interobserver agreement for automated tracking was excellent for NFV assessment (intra- and interobserver, ICC ≥ 0.99) and strong to excellent for regurgitant fraction assessment (intraobserver, ICC ≥ 0.94; interobserver, ICC ≥ 0.89). Conclusion Automated valve tracking reduces analysis time and improves reliability of valvular flow quantification with four-dimensional flow MRI in patients with acquired or congenital heart disease and in healthy volunteers. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by François in this issue.
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http://dx.doi.org/10.1148/radiol.2018180807DOI Listing
January 2019
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