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Background: Lymphatic disorders such as protein-losing enteropathy, plastic bronchitis, and chylothorax are important complications of the Fontan circulation and ultimately result in an increased risk of early death. Several European centers are now performing lymphatic procedures. The aim of this study is to map the extent of these lymphatic disorders and treatments provided across European pediatric cardiology centers., Methods and Results: A survey was circulated to 49 European pediatric cardiology centers consisting of 37 questions including a mix of binary, categorical, and continuous variables. Thirty-one centers (63%) participated in the study, performing a median of 250 (interquartile range, 178 - 313) cardiopulmonary bypass procedures per year. Chylothorax emerged as the most prevalent lymphatic disorder followed by protein-losing enteropathy and plastic bronchitis. The most common diagnostic investigation method was noncontrast magnetic resonance lymphangiography (52%). Eleven centers (35%) conducted lymphatic interventions with a median of 3 (interquartile range, 1 - 4) procedures per year and 12 (interquartile range, 5 - 15) interventions in total per center., Conclusions: This study confirms the rarity of and variation in treatment approaches for lymphatic disorders across Europe. With at least 11 centers offering lymphatic interventions, the adoption of these procedures is on the rise in Europe. To improve the quality of care and treatment outcomes for these complex patients, it is crucial to consider evidence-based lymphatic diagnostics, interventional lymphatic procedures, and the centralization of services in Europe.

Cardiovascular magnetic resonance (CMR) imaging is recommended in patients with congenital heart disease (CHD) in clinical practice guidelines as the imaging standard for a large variety of diseases. As CMR is evolving, novel techniques are becoming available. Some of them are already used clinically, whereas others still need further evaluation. In this statement the authors give an overview of relevant new CMR techniques for the assessment of CHD. Studies with reference values for these new techniques are listed in the supplement., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Worldwide, 1-2% of children are born premature and at risk for developing bronchopulmonary dysplasia (BPD). Preterm-born adults are at risk for early cardiovascular disease. The role of BPD is unclear. This study aims to examine cardiorespiratory function during submaximal exercise in young adult survivors of extreme prematurity, with or without BPD., Methods: 40 preterm-born young adults, 20 with BPD (median gestational age 27 weeks, interquartile range (IQR) 26-28 weeks) and 20 without BPD (median gestational age 28 weeks, IQR 27-29 weeks) were prospectively compared to age-matched at term-born adults (median gestational age 39 weeks, IQR 38-40 weeks). Participants underwent exercise testing and cardiovascular magnetic resonance with submaximal exercise., Results: Resting heart rate in BPD subjects was higher than in at term-born subjects (69±10 mL versus 61±7 mL, p=0.01). Peak oxygen uptake during maximal cardiopulmonary exercise testing was decreased in BPD subjects (91±18% versus 106±17% of predicted, p=0.01). In BPD subjects, cardiac stroke volume change with exercise was impaired compared to at term-born subjects (11±13% versus 25±10%; p<0.001). With exercise, left ventricular end-diastolic volume decreased more in preterm-born subjects with versus without BPD (-10±8% versus -3±8%; p=0.01) and compared to at term-born subjects (0±5%; p<0.001). Exploratory data analysis revealed that exercise stroke volume and end-diastolic volume change were inversely correlated with oxygen dependency in those born prematurely., Conclusions: In preterm-born young adults, particularly those with BPD, resting cardiac function, exercise performance and cardiac response to exercise is impaired compared to controls. Exercise cardiovascular magnetic resonance may reveal an important predisposition for heart disease later in life., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2024.)

Cardiovascular magnetic resonance (CMR) has become the reference standard for quantitative and qualitative assessment of ventricular function, blood flow, and myocardial tissue characterization. There is a preponderance of large CMR studies and registries in adults; However, similarly powered studies are lacking for the pediatric and congenital heart disease (PCHD) population. To date, most CMR studies in children are limited to small single or multicenter studies, thereby limiting the conclusions that can be drawn. Within the PCHD CMR community, a collaborative effort has been successfully employed to recognize knowledge gaps with the aim to embolden the development and initiation of high-quality, large-scale multicenter research. In this publication, we highlight the underlying challenges and provide a practical guide toward the development of larger, multicenter initiatives focusing on PCHD populations, which can serve as a model for future multicenter efforts., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Michael DiLorenzo reports a relationship with GE Healthcare that includes: funding grants. Mark Fogel reports a relationship with Rocket Pharmaceuticals Inc that includes: consulting or advisory. Mark Fogel reports a relationship with CMP Pharma that includes: funding grants. Andrew Powell reports a relationship with Siemens Medical Solutions USA Inc that includes: consulting or advisory. Shaine Morris reports a relationship with Aytu BioPharma Inc that includes: non-financial support. Kanwal Farooqi reports a relationship with Bristol-Myers Squibb Foundation that includes: funding grants. Jonathan Soslow reports a relationship with Pfizer Inc that includes: consulting or advisory. Jonathan Soslow reports a relationship with Sarepta Therapeutics Inc that includes: consulting or advisory. Jonathan Soslow reports a relationship with Immunoforge that includes: consulting or advisory. Heynric Grotenhuis serves as an associate editor for JCMR. Mark Fogel and Andrew Powell serve as members of the editorial board for JCMR. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: Effective therapy to improve exercise capacity in Fontan patients is lacking. Leg-focused high-weight resistance training might augment the peripheral muscle pump and thereby improve exercise capacity., Methods and Results: This randomized semi-cross-over controlled trial investigated the effects of a 12-week leg-focused high-weight resistance training plus high-protein diet, on (sub)maximal exercise capacity, cardiac function (assessed with cardiovascular magnetic resonance), muscle strength, and quality of life in paediatric Fontan patients. Twenty-eight paediatric Fontan patients were included, 27 patients, (median age 12.9 [10.5-15.7]), and successfully completed the programme. Peak oxygen uptake (PeakVO2) at baseline was reduced [33.3 mL/kg/min (27.1-37.4), 73% (62-79) of predicted]. After training PeakVO2/kg and Peak workload improved significantly with +6.2 mL/kg/min (95%CI: 3.4-9.0) (+18%) P < 0.001 and +22 Watts (95%CI: 12-32) (+18%) P < 0.001, respectively, compared to the control period. Indexed single ventricle stroke volume increased significantly [43 mL/beat/m2 (40-49) vs. 46 (41-53), P = 0.014], as did inferior vena cava flow [21 mL/beat/m2 (18-24) vs. 23 (20-28), P = 0.015], while superior vena cava flow remained unchanged. The strength of all measured leg-muscles increased significantly compared to the control period. Self-reported quality of life improved on the physical functioning and change in health domains of the child health questionnaire, parent-reported quality of life improved the bodily pain, general health perception, and change in health domains compared to the control period., Conclusion: In a relatively large group of 27 older Fontan children, 12-weeks of leg-focused high-weight resistance training improved exercise capacity, stroke volume, (sub)maximal exercise capacity, muscle strength, and domains of quality of life., Registration: International Clinical Trials: Trial NL8181., Competing Interests: Conflict of interest: Authors have no conflicts of interest to declare that are relevant to the content of this article., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: Congenital supravalvular aortic stenosis (SVAS) is a rare form of congenital outflow tract obstruction and long-term outcomes are scarcely reported. This study aims to provide an overview of outcomes after surgical repair for congenital SVAS., Methods: A systematic review of published literature was conducted, including observational studies reporting long-term clinical outcome (>2 years) after SVAS repair in children or adults considering >20 patients. Early risks, late event rates and time-to-event data were pooled and entered into a microsimulation model to estimate 30-year outcomes. Life expectancy was compared to the age-, sex- and origin-matched general population., Results: Twenty-three publications were included, encompassing a total of 1472 patients (13 125 patient-years; pooled mean follow-up: 9.0 (6.2) years; median follow-up: 6.3 years). Pooled mean age at surgical repair was 4.7 (5.8) years and the most commonly used surgical technique was the single-patch repair (43.6%). Pooled early mortality was 4.2% (95% confidence interval: 3.2-5.5%) and late mortality was 0.61% (95% CI: 0.45-0.83) per patient-year. Based on microsimulation, over a 30-year time horizon, it was estimated that an average patient with SVAS repair (mean age: 4.7 years) had an observed life expectancy that was 90.7% (95% credible interval: 90.0-91.6%) of expected life expectancy in the matched general population. The microsimulation-based 30-year risk of myocardial infarction was 8.1% (95% credible interval: 7.3-9.9%) and reintervention 31.3% (95% credible interval: 29.6-33.4%), of which 27.2% (95% credible interval: 25.8-29.1) due to repair dysfunction., Conclusions: After surgical repair for SVAS, 30-year survival is lower than the matched-general-population survival and the lifetime risk of reintervention is considerable. Therefore, lifelong monitoring of the cardiovascular system and in particular residual stenosis and coronary obstruction is recommended., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Introduction: The aims of this study were to provide an overview of the cardiac stress response in Fontan patients and of the use, safety and clinical value of stress imaging in Fontan patients., Methods: Studies evaluating cardiac function using stress imaging in Fontan patients published up until 12 December 2021 were included in this review., Results: From 1603 potential studies, 32 studies met the inclusion criteria. In total, stress imaging tests of 728 Fontan patients were included. Cardiac function was most often measured using physical stress (61%), all other studies used dobutamine-induced stress. Stroke volume (SV) increased in most studies (71%), mean SV at rest ranged from 27 mL/m 2 to 60 mL/m 2 versus 27 mL/m 2 to 101 mL/m 2 during stress, and increased with an average of 4%. Ejection fraction increased in almost all studies, whereas both end-systolic volume and end-diastolic volume decreased during stress. Higher heart rates were obtained with physical stress (82-180) compared to dobutamine induced stress (73-128). Compared to controls, increases in heartrate and SV were lower and end-diastolic volume decreased abnormally in 75% of reporting studies. No major adverse events were reported. Poorer cardiac stress response was related to decreased exercise capacity and higher risk for long-term (adverse) outcomes in Fontan patients., Discussion: Cardiac stress response in Fontan patients differs from healthy subjects, reflected by lower increases in heart rate, diminished preload and decreased cardiac output, especially during higher levels of exercise. Stress imaging is safe, however the added clinical value needs to be investigated in more detail., (Copyright © 2023 ErasmusMC-Sophia children's hospital, Rotterdam, the Netherlands. Published by Elsevier B.V. All rights reserved.)

Background: Optimal timing of pulmonary valve replacement (PVR) in Tetralogy of Fallot (TOF) patients remains challenging. Ventricular wall stress is considered to be an early marker of right ventricular (RV) dysfunction., Objectives: To investigate the association of RV wall stresses and their change over time with functional parameters in TOF patients., Methods: Ten TOF patients after surgical repair with moderate/severe pulmonary regurgitation were included. At two timepoints (median follow-up time 7.2 years), patient-specific computational biventricular models for wall stress assessment were created using CMR short-axis cine images and echocardiography-based RV pressures. RV ejection fraction (RVEF), NT-proBNP and cardiopulmonary exercise tests were used as outcome measures reflecting RV function. Associations between regional RV diastolic wall stress and RV function were investigated using linear mixed models., Results: Increased wall stress correlated with lower RV mass ( r rm  = -0.70, p  = 0.017) and lower RV mass-to-volume ( r  = 0.003) using repeated measures. Wall stress decreased significantly over time, especially in patients with a stable RVEF ( rm  = -0.80, p  = 0.003) using repeated measures. Wall stress decreased significantly over time, especially in patients with a stable RVEF ( p  < 0.001). Higher wall stress was independently associated with lower RVEF, adjusted for left ventricular ejection fraction, RV end-diastolic volume and time since initial surgery (decrease of 1.27% RVEF per kPa increase in wall stress, p  = 0.029) using repeated measurements. No association was found between wall stress, NT-proBNP, and exercise capacity., Conclusions: Using a computational method to calculate wall stress locally in geometrically complex ventricles, we demonstrated that lower wall stress might be important to maintain ventricular function. RV wall stress assessment can be used in serial follow-up, and is potentially an early marker of impending RV dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Minderhoud, Hirsch, Marin, Kardys, Rodríguez-Matas, Chiastra, Roos-Hesselink, Wentzel, Helbing and Akyildiz.)

Fontan circulation is a highly abnormal circulatory state that may affect various organ systems. The effect on body composition is an important factor to assess the condition of the patient. This systematic review assesses body composition and possibly related adverse outcomes in patients with a Fontan circulation, to provide an overview of current insights. Studies evaluating body composition by compartment (either fat mass or lean/muscle mass) in Fontan patients published up to April 2023 were included in this systematic review. Of 1392 potential studies, 18 studies met the inclusion criteria. In total, body composition measurements of 774 Fontan patients were included. Body composition was measured using dual-energy X-ray absorptiometry (DXA) (n = 12), bioelectrical impedance analysis (BIA) (n = 5), computer tomography (CT) (n = 1), or magnetic resonance imaging (MRI) (n = 1). All studies reported a normal body mass index (BMI) in Fontan patients, compared to controls. Five out of nine studies reported significantly higher body fat values, and twelve out of fifteen studies reported significantly lower muscle or lean mass values in the Fontan population compared to the healthy population. Unfavorable body composition in Fontan patients was associated with decreased exercise capacity, worse cardiac function, and adverse outcomes including hospital admissions and death.   Conclusions: Despite having a normal BMI, Fontan patients have an increased fat mass and decreased muscle mass or lean mass compared to the healthy population. This unfavorable body composition was associated with various adverse outcomes, including a decreased exercise capacity and worse cardiac function. What is Known: • Patients with a Fontan circulation have a decreased exercise capacity compared to healthy peers, an unfavorable body composition might be a contributor to their impaired exercise capacity. What is New: • Fontan patients are predisposed to an unfavorable body composition, characterized by increased fat mass and decreased muscle mass accompanied by a normal BMI compared to the healthy population. • Among others, unfavorable body composition was associated with decreased exercise capacity, cardiac function, and increased morbidity in patients with a Fontan circulation., (© 2023. The Author(s).)

Background: Left ventricular (LV) strain and rotation are emerging functional markers for early detection of LV dysfunction and have been associated with the burden of myocardial fibrosis in several disease states. This study examined the association between LV deformation (i.e., LV strain and rotation) and extent and location of LV myocardial fibrosis in pediatric patients with Duchenne muscular dystrophy (DMD)., Methods and Results: 34 pediatric patients with DMD underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) to assess LV myocardial fibrosis. Offline CMR feature-tracking analysis was used to assess global and segmental longitudinal and circumferential LV strain, and LV rotation. Patients with fibrosis (n = 18, 52.9%) were older than those without fibrosis (14 ± 3 years (yrs) vs 11 ± 2 yrs., p = 0.01). There was no significant difference in LV ejection fraction (LVEF) between subjects with and without fibrosis (54 ± 6% vs 56 ± 4%, p = 0.18). However, lower endocardial global circumferential strain (GCS), but not LV rotation, was associated with presence of fibrosis (adjusted Odds Ratio 1.25 [95% CI 1.01-1.56], p = 0.04). Both GCS and global longitudinal strain correlated with the extent of fibrosis (r = .52, p = 0.03 and r = .75, p < 0.01, respectively). Importantly, segmental strain did not seem to correspond to location of fibrosis., Conclusion: A lower global, but not segmental, strain is associated with presence and extent of LV myocardial fibrosis in pediatric DMD patients. Therefore, strain parameters might detect structural myocardial alterations, however currently more research is needed to evaluate its value (e.g., prognostic) in clinical practice., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: To support decision-making in children undergoing aortic valve replacement (AVR), by providing a comprehensive overview of published outcomes after paediatric AVR, and microsimulation-based age-specific estimates of outcome with different valve substitutes., Methods and Results: A systematic review of published literature reporting clinical outcome after paediatric AVR (mean age <18 years) published between 1/1/1990 and 11/08/2021 was conducted. Publications reporting outcome after paediatric Ross procedure, mechanical AVR (mAVR), homograft AVR (hAVR), and/or bioprosthetic AVR were considered for inclusion. Early risks (<30d), late event rates (>30d) and time-to-event data were pooled and entered into a microsimulation model. Sixty-eight studies, of which one prospective and 67 retrospective cohort studies, were included, encompassing a total of 5259 patients (37 435 patient-years; median follow-up: 5.9 years; range 1-21 years). Pooled mean age for the Ross procedure, mAVR, and hAVR was 9.2 ± 5.6, 13.0 ± 3.4, and 8.4 ± 5.4 years, respectively. Pooled early mortality for the Ross procedure, mAVR, and hAVR was 3.7% (95% CI, 3.0%-4.7%), 7.0% (5.1%-9.6%), and 10.6% (6.6%-17.0%), respectively, and late mortality rate was 0.5%/year (0.4%-0.7%/year), 1.0%/year (0.6%-1.5%/year), and 1.4%/year (0.8%-2.5%/year), respectively. Microsimulation-based mean life-expectancy in the first 20 years was 18.9 years (18.6-19.1 years) after Ross (relative life-expectancy: 94.8%) and 17.0 years (16.5-17.6 years) after mAVR (relative life-expectancy: 86.3%). Microsimulation-based 20-year risk of aortic valve reintervention was 42.0% (95% CI: 39.6%-44.6%) after Ross and 17.8% (95% CI: 17.0%-19.4%) after mAVR., Conclusion: Results of paediatric AVR are currently suboptimal with substantial mortality especially in the very young with considerable reintervention hazards for all valve substitutes, but the Ross procedure provides a survival benefit over mAVR. Pros and cons of substitutes should be carefully weighed during paediatric valve selection., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: To support clinical decision-making in children with aortic valve disease, by compiling the available evidence on outcome after paediatric aortic valve repair (AVr)., Methods: A systematic review of literature reporting clinical outcome after paediatric AVr (mean age at surgery <18 years) published between 1 January 1990 and 23 December 2021 was conducted. Early event risks, late event rates and time-to-event data were pooled. A microsimulation model was employed to simulate the lives of individual children, infants and neonates following AVr., Results: Forty-one publications were included, encompassing 2 623 patients with 17 217 patient-years of follow-up (median follow-up: 7.3 years; range: 1.0-14.4 years). Pooled mean age during repair for aortic stenosis in children (<18 years), infants (<1 year) or neonates (<30 days) was 5.2 ± 3.9 years, 35 ± 137 days and 11 ± 6 days, respectively. Pooled early mortality after stenosis repair in children, infants and neonates, respectively, was 3.5% (95% confidence interval: 1.9-6.5%), 7.4% (4.2-13.0%) and 10.7% (6.8-16.9%). Pooled late reintervention rate after stenosis repair in children, infants and neonates, respectively, was 3.31%/year (1.66-6.63%/year), 6.84%/year (3.95-11.83%/year) and 6.32%/year (3.04-13.15%/year); endocarditis 0.07%/year (0.03-0.21%/year), 0.23%/year (0.07-0.71%/year) and 0.49%/year (0.18-1.29%/year); and valve thrombosis 0.05%/year (0.01-0.26%/year), 0.15%/year (0.04-0.53%/year) and 0.19%/year (0.05-0.77%/year). Microsimulation-based mean life expectancy in the first 20 years for children, infants and neonates with aortic stenosis, respectively, was 18.4 years (95% credible interval: 18.1-18.7 years; relative survival compared to the matched general population: 92.2%), 16.8 years (16.5-17.0 years; relative survival: 84.2%) and 15.9 years (14.8-17.0 years; relative survival: 80.1%). Microsimulation-based 20-year risk of reintervention in children, infants and neonates, respectively, was 75.2% (72.9-77.2%), 53.8% (51.9-55.7%) and 50.8% (47.0-57.6%)., Conclusions: Long-term outcomes after paediatric AVr for stenosis are satisfactory and dependent on age at surgery. Despite a high hazard of reintervention for valve dysfunction and slightly impaired survival relative to the general population, AVr is associated with low valve-related event occurrences and should be considered in children with aortic valve disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Manually segmenting cardiac structures is time-consuming and produces variability in MRI assessments. Automated segmentation could solve this. However, current software is developed for adults without congenital heart defects (CHD)., Purpose: To evaluate automated segmentation of left ventricle (LV) and right ventricle (RV) for pediatric MRI studies., Study Type: Retrospective comparative study., Population: Twenty children per group of: healthy children, LV-CHD, tetralogy of Fallot (ToF), and univentricular CHD, aged 11.7 [8.9-16.0], 14.2 [10.6-15.7], 14.6 [11.6-16.4], and 12.2 [10.2-14.9] years, respectively., Sequence/field Strength: Balanced steady-state free precession at 1.5 T., Assessment: Biventricular volumes and masses were calculated from a short-axis stack of images, which were segmented manually and using two fully automated software suites (Medis Suite 3.2, Medis, Leiden, the Netherlands and SuiteHeart 5.0, Neosoft LLC, Pewaukee, USA). Fully automated segmentations were manually adjusted to provide two further sets of segmentations. Fully automated and adjusted automated segmentation were compared to manual segmentation. Segmentation times and reproducibility for each method were assessed., Statistical Tests: Bland Altman analysis and intraclass correlation coefficients (ICC) were used to compare volumes and masses between methods. Postprocessing times were compared by paired t-tests., Results: Fully automated methods provided good segmentation (ICC > 0.90 compared to manual segmentation) for the LV in the healthy and left-sided CHD groups (eg LV-EDV difference for healthy children 1.4 ± 11.5 mL, ICC: 0.97, for Medis and 3.0 ± 12.2 mL, ICC: 0.96 for SuiteHeart). Both automated methods gave larger errors (ICC: 0.62-0.94) for the RV in these populations, and for all structures in the ToF and univentricular CHD groups. Adjusted automated segmentation agreed well with manual segmentation (ICC: 0.71-1.00), improved reproducibility and reduced segmentation time in all patient groups, compared to manual segmentation., Data Conclusion: Fully automated segmentation eliminates observer variability but may produce large errors compared to manual segmentation. Manual adjustments reduce these errors, improve reproducibility, and reduce postprocessing times compared to manual segmentation. Adjusted automated segmentation is reasonable in children with and without CHD., Evidence Level: 3., Technical Efficacy: Stage 2., (© 2022 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objective: Children and adults with repaired tetralogy of Fallot (rTOF) have an impaired exercise capacity, a less active lifestyle and an increased long-term risk of adverse outcomes compared with healthy peers. This study aimed to summarise the current evidence for the effectiveness and safety of exercise training interventions in patients with rTOF., Methods: PubMed/MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus and reference lists of relevant articles were searched for prospective studies published by November 2021. Random-effects meta-analysis and descriptive synthesis were performed to assess the effectiveness and safety of exercise training in patients with rTOF., Results: Of the 9677 citations identified, 12 articles were included that reported on 10 unique studies and covered 208 patients with rTOF (range of mean/median age: 7.4-43.3 years). All studies implemented 2 to 7 aerobic or respiratory training sessions per week with durations ranging from 6 to 26 weeks. Meta-analysis of the included randomised controlled trials showed that exercise training was associated with a significant improvement in peak VO 2 (pooled mean difference: +3.1 mL/min/kg; 95% CI: 0.76 to 5.36 mL/min/kg, p=0.019). Cardiac imaging studies revealed no subclinical adverse remodelling after the exercise interventions. No serious adverse events including arrhythmias were reported in these studies., Conclusion: Current evidence suggests that exercise training can improve exercise capacity in patients with rTOF with a low risk for adverse events. Exercise prescription may be a safe and effective tool to help improving outcomes in patients with rTOF., Prospero Registration Number: CRD42021292809., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Cardiac surgery may cause temporarily impaired ventricular performance and myocardial injury. We aim to characterise the response to perioperative injury for patients undergoing repair or pulmonary valve replacement (PVR) for tetralogy of Fallot (ToF)., Methods: We enrolled children undergoing ToF repair or PVR from four tertiary centres in a prospective observational study. Assessment-including blood sampling and speckle tracking echocardiography-occurred before surgery (T1), at the first follow-up (T2) and 1 year after the procedures (T3). Ninety-two serum biomarkers were expressed as principal components to reduce multiple statistical testing. RNA Sequencing was performed on right ventricular (RV) outflow tract samples., Results: We included 45 patients with ToF repair aged 4.3 (3.4 - 6.5) months and 16 patients with PVR aged 10.4 (7.8 - 12.7) years. Ventricular function following ToF repair showed a fall-and-rise pattern for left ventricular global longitudinal strain (GLS) (-18±4 to -13±4 to -20±2, p < 0.001 for each comparison) and RV GLS (-19±5 to -14±4 to 20±4, p < 0.002 for each comparison). This pattern was not seen for patients undergoing PVR. Serum biomarkers were expressed as three principal components. These phenotypes are related to: (1) surgery type, (2) uncorrected ToF and (3) early postoperative status. Principal component 3 scores were increased at T2. This increase was higher for ToF repair than PVR. The transcriptomes of RV outflow tract tissue are related to patients' sex, rather than ToF-related phenotypes in a subset of the study population., Conclusions: The response to perioperative injury following ToF repair and PVR is characterised by specific functional and immunological responses. However, we did not identify factors relating to (dis)advantageous recovery from perioperative injury., Trial Registration Number: Netherlands Trial Register: NL5129., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Right ventricular dysfunction is a major determinant of outcome in patients with complex congenital heart disease, as in tetralogy of Fallot. In these patients, right ventricular dysfunction emerges after initial pressure overload and hypoxemia, which is followed by chronic volume overload due to pulmonary regurgitation after corrective surgery. Myocardial adaptation and the transition to right ventricular failure remain poorly understood. Combining insights from clinical and experimental physiology and myocardial (tissue) data has identified a disease phenotype with important distinctions from other types of heart failure. This phenotype of the right ventricle in tetralogy of Fallot can be described as a syndrome of dysfunctional characteristics affecting both contraction and filling. These characteristics are the end result of several adaptation pathways of the cardiomyocytes, myocardial vasculature and extracellular matrix. As long as the long-term outcome of surgical correction of tetralogy of Fallot remains suboptimal, other treatment strategies need to be explored. Novel insights in failure of adaptation and the role of cardiomyocyte proliferation might provide targets for treatment of the (dysfunctional) right ventricle under stress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Alipour Symakani, van Genuchten, Zandbergen, Henry, Taverne, Merkus, Helbing and Bartelds.)

In patients with congenital heart disease (CHD), reduced exercise capacity can be a predictor for late complications and may be used to guide interventions. Yet, the interpretation of exercise capacity is challenged by changes in body composition during growth. Our aim was to create an overview of disease-specific exercise capacity in children with CHD. We performed a multicentre retrospective study of exercise capacity of CHD patients, aged 6-18 years, tested between January 2001 and October 2018. Sex-specific distribution graphs were made using the LMS method and height to relate to body size. We included all CHD with N > 50, including severe defects (e.g., univentricular heart, tetralogy of Fallot) and "simple" lesions as ventricular septum defect and atrial septum defect. We included 1383 tests of 1208 individual patients for analysis. The peak oxygen uptake (VO 2 peak, 37.3 ml/min/kg (25th-75th percentile 31.3-43.8)) varied between specific defects; patients with univentricular hearts had lower VO 2peak compared with other CHD. All groups had lower VO 2peak compared to healthy Dutch children. Males had higher VO 2peak , W peak and O 2 pulse peak than females. Sex- and disease-specific distribution graphs for VO 2peak , W peak and O2pulse peak showed increase in variation with increase in height.   Conclusion: Disease-specific distribution graphs for exercise capacity in children with CHD from a large multicentre cohort demonstrated varying degrees of reduced VO 2peak and W peak . The distribution graphs can be used in the structured follow-up of patients with CHD to predict outcome and identify patients at risk. What is Known: • Children with congenital heart disease (COnHD) are at risk to develop heart failure, arrhytmia's and other complications. Exercise capacity may be an important predictor for outcome in children with ConHD. In children, the interpretation of exercise capacity poses an additional challenge related to physical changes during growth. What is New: • In this report of a multi-center cohort >1300 childrewn with ConHD, we related the changes in exercise capacity to length. We demonstrated that exercise capacity was reduced as compared with healthy children and we observed variation between disease groups. Patients with a univentricular circulation (Fontan) had worse exercise capacity. We constructed disease specific charts of development of exercise capacity throughout childhood, accessible via a web-site. These graphs may help practitioner to guide children with ConHD., (© 2022. The Author(s).)

Background: Cardiovascular magnetic resonance (CMR) imaging during supine exercise at (sub)maximal oxygen consumption (VO 2 ) offers unique diagnostic insights. However, maximal VO 2 is not achievable in the supine position and standardizing submaximal exercise intensities remains challenging. Using heart rate or workload could be a viable option to translate VO 2 -based submaximal exercise intensities., Aim: To translate submaximal exercise intensities upright cycling exercise (UCE) to supine push-pull exercise (SPPE), by comparing heart rate or workload determined during UCE, with heart rate and workload during SPPE at similar exercise intensities., Methods and Results: Sixteen healthy young adults (20.4 ± 2.2 years; 8 female) underwent cardiopulmonary UCE and SPPE testing [mean ± standard deviation maximal VO 2 : 3.2 ± 0.6 vs. 5 ± 0.3 L min -1 , p < 0.001 and median (interquartile range) of the maximum workload: 310 (244, 361) vs. 98 (98, 100), p < 0.001, respectively]. Heart rate at 40% and 60% of maximal VO 2 , as determined by UCE, showed low bias (-3 and 0 bpm, respectively) and wide limits of agreement (±26 and ±28 bpm, respectively), in Bland-Altman analysis. VO 2 /Workload relation was exponential and less efficient during SPPE compared to UCE. Generalized estimated equation analysis predicted model-based mean workload during SPPE, with acceptable 95% confidence interval., Conclusion: Heart rate during UCE at submaximal exercise intensities can reasonably well be used to for SPPE in healthy subjects. Using workload, an ergometer specific, model-based mean can be used to determine exercise intensities during SPPE. Individual variations in response to posture and movement change are high. During clinical interpretation of exercise CMR, individual exercise intensity has to be considered., (© 2022 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

With the trend towards childhood surgery in patients with Ebstein anomaly (EA), thorough imaging is crucial for patient selection. This study aimed to assess biventricular function by echocardiography and cardiac magnetic resonance (CMR) and compare EA severity classifications. Twenty-three patients (8-17 years) underwent echocardiography and CMR. Echocardiographic parameters included tricuspid annular plane systolic excursions (TAPSE), fractional area change of the functional right ventricle (fRV-FAC), fRV free wall peak systolic myocardial velocity (fRVs'), and tricuspid regurgitation (TR). End-diastolic and end-systolic volume (EDV resp. ESV), fRV- and LV ejection fraction (EF) and TR were obtained by CMR. EA severity classifications included displacement index, Celermajer index and the total-right/left-volume index. Median fRV-FAC was 38% (IQR 33-42). TAPSE and fRVs' were reduced in 39% and 75% of the patients, respectively. Echocardiographic TR was visually graded as mild, moderate, or severe in nine, six and eight patients, respectively. By CMR, median fRVEF was 49% (IQR 36-58) and TR was graded as mild, moderate, or severe in nine, twelve and two patients, respectively. In 70% of cases, fRV-EDV was higher than LV-EDV. LVEF was decreased in 17 cases (74%). There was excellent correlation between echocardiography-derived fRV-FAC and CMR-derived fRVEF (rho = 0.812, p < 0.001). While echocardiography is a versatile tool in the complex geometry of the Ebstein heart, it has limitations. CMR offers a total overview and has the advantage of reliable volume assessment of both ventricles. Comprehensive evaluation of pediatric patients with EA may therefore require a synergistic implementation of echocardiography and CMR., (© 2022. The Author(s).)

Background Ventricular performance is temporarily reduced following surgical atrial septal defect closure. Cardiopulmonary bypass and changes in loading conditions are considered important factors, but this phenomenon is incompletely understood. We aim to characterize biventricular performance following surgical and percutaneous atrial septal defect closure and to relate biomarkers to ventricular performance following intervention. Methods and Results In this multicenter prospective study, children scheduled for surgical or percutaneous atrial septal defect closure were included. Subjects were assessed preoperatively, in the second week postintervention (at 2-weeks follow-up), and 1-year postintervention (1-year follow-up). At each time point, an echocardiographic study and a panel of biomarkers were obtained. Sixty-three patients (median age, 4.1 [interquartile range, 3.1-6.1] years) were included. Forty-three patients underwent surgery. At 2-weeks follow-up, right ventricular global longitudinal strain was decreased for the surgical, but not the percutaneous, group (-17.6±4.1 versus -27.1±3.4; P <0.001). A smaller decrease was noted for left ventricular global longitudinal strain at 2-weeks follow-up for the surgical group (surgical versus percutaneous, -18.6±3.2 versus -20.2±2.4; P =0.040). At 1-year follow-up, left ventricular performance returned to baseline, whereas right ventricular performance improved, but did not reach preintervention levels. Eight biomarkers relating to cardiovascular and immunological processes differed across study time points. Of these biomarkers, only NT-proBNP (N-terminal pro-B-type natriuretic peptide) correlated with less favorable left ventricular global longitudinal strain at 2-weeks follow-up. Conclusions Right, and to a lesser degree left, ventricular performance was reduced early after surgical atrial septal defect closure. Right ventricular performance at 1-year follow-up remained below baseline levels. Several biomarkers showed a pattern over time similar to ventricular performance. These biomarkers may provide insight into the processes that affect ventricular function. Registration URL: https://www.trialregister.nl/; Unique identifier: NL5129.

Background: To determine the potential prognostic value and clinical correlations of blood biomarkers in a cohort of patients with Tetralogy of Fallot (TOF)., Methods: In the setting of multicenter prospective research studies TOF patients underwent blood sampling, cardiopulmonary exercise testing and low-dose dobutamine stress cardiac magnetic resonance (CMR) imaging. In the blood sample NT-proBNP, GDF-15, Galectin-3, ST-2, DLK-1, FABP4, IGFBP-1, IGFBP-7, MMP-2, and vWF were assessed. During subsequent follow-up, patients were evaluated for reaching the study endpoint (cardiac death, arrhythmia-related hospitalization or cardioversion/ablation, VO 2 max ≤65% of predicted). Regression analysis was used to explore the correlation between blood biomarkers (corrected for age and gender) and other clinical parameters. The potential predictive value of blood biomarkers and events were assessed with Kaplan-Meier analysis and Cox proportional hazard analysis., Results: We included 137 Fallot patients, median age 19.2 (interquartile range: 14.6-25.7) years, median age at TOF-repair 0.9 (0.5-1.9) years. After a median follow-up of 8.7 (6.3-10.7) years, 20 (14.6%) patients reached the composite endpoint. In a multivariable cox-regression analysis corrected for age at study baseline, elevated IGFBP-7 and MMP-2 levels were associated with the composite endpoint. We also noted a correlation between DLK-1 and relative change in right ventricular end systolic volume during dobutamine stress CMR (β = -0.27, p = 0.010), a correlation between FABP4 and Max VO 2 (β = -0.41, p ≤0.001 and between MMP-2 and tricuspid valve E/A ratio (β = -0.15, p = 0.037)., Conclusions: IGFBP-7, MMP-2 and DLK-1 levels are related to cardiac function and long-term outcome in TOF patients., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: To examine whether maternal angiogenic factors in the first half of pregnancy are associated with offspring left and right cardiac development., Methods: In a population-based prospective cohort among 2,415 women and their offspring, maternal first and second trimester plasma PlGF and sFlt-1 concentrations were measured. Cardiac MRI was performed in their offspring at 10 years., Results: Maternal angiogenic factors were not associated with childhood cardiac outcomes in the total population. In children born small-for-their-gestational-age, higher maternal first trimester PlGF concentrations were associated with a lower childhood left ventricular mass  (-0.24 SDS  [95%CI -0.42, -0.05 per SDS increase in maternal PlGF]), whereas higher sFlt-1 concentrations were associated with higher childhood left ventricular mass  (0.22 SDS  [95%CI 0.09, 0.34 per SDS increase in maternal sFlt-1]). Higher second trimester maternal sFlt-1 concentrations were also associated with higher childhood left ventricular mass  (P-value <.05). In preterm born children, higher maternal first and second trimester sFlt-1/PlGF ratio were associated with higher childhood left ventricular mass  (0.30 SDS  [95%CI 0.01, 0.60], 0.22 SDS  [95%CI -0.03, 0.40]) per SDS increase in maternal sFlt-1/PlGF ratio in first and second trimester respectively). No effects on other childhood cardiac outcomes were present within these higher-risk children., Conclusions: In a low-risk population, maternal angiogenic factors are not associated with childhood cardiac ventricular structure, and function within the normal range. In children born small for their gestational age or preterm, an imbalance in maternal angiogenic factors in the first half of pregnancy was associated with higher childhood left ventricular mass only., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Neonates with critical congenital heart disease (CCHD) undergoing cardiac surgery with cardiopulmonary bypass (CPB) are at risk of brain injury that may result in adverse neurodevelopment. To date, no therapy is available to improve long-term neurodevelopmental outcomes of CCHD neonates. Allopurinol, a xanthine oxidase inhibitor, prevents the formation of reactive oxygen and nitrogen species, thereby limiting cell damage during reperfusion and reoxygenation to the brain and heart. Animal and neonatal studies suggest that allopurinol reduces hypoxic-ischemic brain injury and is cardioprotective and safe. This trial aims to test the hypothesis that allopurinol administration in CCHD neonates will result in a 20% reduction in moderate to severe ischemic and hemorrhagic brain injury., Methods: This is a phase III, randomized, quadruple-blinded, placebo-controlled, multicenter trial. Neonates with a prenatal or postnatal CCHD diagnosis requiring cardiac surgery with CPB in the first 4 weeks after birth are eligible to participate. Allopurinol or mannitol-placebo will be administered intravenously in 2 doses early postnatally in neonates diagnosed antenatally and 3 doses perioperatively of 20 mg/kg each in all neonates. The primary outcome is a composite endpoint of moderate/severe ischemic or hemorrhagic brain injury on early postoperative MRI, being too unstable for postoperative MRI, or mortality within 1 month following CPB. A total of 236 patients (n = 188 with prenatal diagnosis) is required to demonstrate a reduction of the primary outcome incidence by 20% in the prenatal group and by 9% in the postnatal group (power 80%; overall type 1 error controlled at 5%, two-sided), including 1 interim analysis at n = 118 (n = 94 with prenatal diagnosis) with the option to stop early for efficacy. Secondary outcomes include preoperative and postoperative brain injury severity, white matter injury volume (MRI), and cardiac function (echocardiography); postnatal and postoperative seizure activity (aEEG) and regional cerebral oxygen saturation (NIRS); neurodevelopment at 3 months (general movements); motor, cognitive, and language development and quality of life at 24 months; and safety and cost-effectiveness of allopurinol., Discussion: This trial will investigate whether allopurinol administered directly after birth and around cardiac surgery reduces moderate/severe ischemic and hemorrhagic brain injury and improves cardiac function and neurodevelopmental outcome in CCHD neonates., Trial Registration: EudraCT 2017-004596-31. Registered on November 14, 2017. ClinicalTrials.gov NCT04217421. Registered on January 3, 2020., (© 2022. The Author(s).)

Introduction: Physical activity is associated with many physiological and psychological health benefits across the lifespan. Children with a chronic disease often have lower levels of daily physical activity, and a decreased exercise capacity compared to healthy peers. In order to learn more about limitations for physical activity, we investigate children with four different chronic diseases: children with a Fontan circulation, children with Broncho Pulmonary Dysplasia (BPD), Pompe disease and inflammatory bowel disease (IBD). Each of these diseases is likely to interfere with physical activity in a different way. Knowing the specific limitations for physical activity would make it possible to target these, and increase physical activity by a personalized intervention. The aim of this study is to first investigate limitations for physical activity in children with various chronic diseases. Secondly, to measure the effects of a tailored exercise intervention, possibly including a personalized dietary advice and/or psychological counseling, on exercise capacity, endurance, quality of life, fatigue, fear for exercise, safety, muscle strength, physical activity levels, energy balance, and body composition. Methods and Analysis: This randomized crossover trial will aim to include 72 children, aged 6-18 years, with one of the following diagnosis: a Fontan circulation, BPD, Pompe disease and IBD. Eligible patients will participate in the 12-week tailored exercise intervention and are either randomized to start with a control period or start with the intervention. The tailored 12-week exercise interventions, possibly including a personalized dietary advice and/or psychological counseling, will be designed based on the found limitations for physical activity in each disease group during baseline measurements by the Rotterdam Exercise Team. Effects of the tailored training interventions will be measured on the following endpoints: exercise capacity (measured by cardiopulmonary exercise test), endurance, physical activity levels, muscle strength, quality of life, fatigue, fear for exercise, disease activity, cardiac function (in children with a Fontan circulation), energy balance, and body composition. Ethics and Dissemination: Conducted according to the Declaration of Helsinki and Good Clinical Practice. Medical-ethical approval was obtained. Trial Registration Number: NL8181, https://www.trialregister.nl/trial/8181., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Scheffers, Helbing, Utens, Dieleman, Dulfer, Noske, van den Broek, Walet, Olieman, Escher, Pijnenburg, van der Ploeg and van den Berg.)

Aims: To study flow-related energetics in multiple anatomical segments of the total cavopulmonary connection (TCPC) in Fontan patients from four-dimensional (4D) flow magnetic resonance imaging (MRI), and to study the relationship between adverse flow patterns and segment-specific energetics., Methods and Results: Twenty-six extracardiac Fontan patients underwent 4D flow MRI of the TCPC. A segmentation of the TCPC was automatically divided into five anatomical segments [conduit, superior vena cava (SVC), right/left pulmonary artery (LPA), and the Fontan confluence]. The presence of vortical flow in the pulmonary arteries or Fontan confluence was qualitatively scored. Kinetic energy (KE), viscous energy loss rate, and vorticity were calculated from the 4D flow MRI velocity field and normalized for segment length and/or inflow. Energetics were compared between segments and the relationship between vortical flow and segment cross-sectional area (CSA) with segment-specific energetics was determined. Vortical flow in the LPA ( n = 6) and Fontan confluence ( n = 12) were associated with significantly higher vorticity ( P = 0.001 and P = 0.015, respectively) and viscous energy loss rate ( P = 0.046 and P = 0.04, respectively) compared to patients without vortical flow. The LPA and conduit segments showed the highest KE and viscous energy loss rate, while most favourable energetics were observed in the SVC. Conduit CSA inversely correlated with KE ( r = -0.614, P = 0.019) and viscous energy loss rate ( r = -0.652, P = 0.011)., Conclusions: Vortical flow in the Fontan confluence and LPA associated with significantly increased viscous energy loss rate. Four-dimensional flow MRI-derived energetics may be used as a screening tool for direct, MRI-based assessment of flow efficiency in the TCPC., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Medical procedures and hospitalizations can be experienced as traumatic and can lead to post-traumatic stress reactions. Eye movement desensitization and reprocessing (EMDR) shows promising results but very few long-term studies have been published. Therefore, our aim was to test the long-term (8 months post-treatment) effectiveness of EMDR in children and adolescents with medically related subthreshold post-traumatic stress disorder (PTSD)., Methods and Results: Seventy-four children (including 39 with congenital or acquired heart disease) aged 4-15 (M = 9.6 years) with subthreshold PTSD after previous hospitalization were included into a parallel group randomized controlled trial. Participants were randomized to EMDR (n = 37) or care-as-usual (CAU) (n = 37; medical care only). The primary outcome was PTSD symptoms of the child. Secondary outcomes were symptoms of depression and blood-injection-injury (BII) phobia, sleep problems, and health-related quality of life (HrQoL) of the child. Assessments of all outcomes were planned at baseline and 8 weeks and 8 months after the start of EMDR/CAU. We hypothesized that the EMDR group would show significantly more improvements on all outcomes over time. Both groups showed improvements over time on child's symptoms of PTSD (only parent report), depression, BII phobia, sleep problems, and most HrQoL subscales. GEE analyses showed no significant differences between the EMDR group (nT2 = 33, nT3 = 30) and the CAU group (nT2 = 35, nT3 = 32) on the primary outcome. One superior effect of EMDR over time was found for reducing parent-reported BII phobia of the child., Conclusion: EMDR did not perform better than CAU in reducing subthreshold PTSD up to 8 months post-treatment in previously hospitalized children. Possible explanations and clinical implications are discussed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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&#95;vol avg systole , KE avg systole , and EL avg systole ) and diastole (vorticity&#95;vol avg diastole , KE avg diastole , and EL avg diastole ). The association between vorticity&#95;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, P < 0.001; diastolic: ρ = 0.81, P < 0.001) and in Fontan patients (systolic: ρ = 0.61, P < 0.001; diastolic: ρ = 0.54, P = 0.002). Healthy subjects showed positive correlation between vorticity&#95;vol versus KE (systole: ρ = 0.96, P < 0.001; diastole: ρ = 0.90, P < 0.001) and EL (systole: ρ = 0.85, P < 0.001; diastole: ρ = 0.84, P < 0.001). Fontan patients showed significantly elevated vorticity&#95;vol compared with healthy subjects (vorticity&#95;vol avg systole : 3.1 [2.3-3.9] vs. 1.7 [1.3-2.4] L/s, P < 0.001; vorticity&#95;vol avg diastole : 3.1 [2.0-3.7] vs. 2.1 [1.6-2.8] L/s, P = 0.002). This elevated vorticity in Fontan patients showed strong association with KE (systole: ρ = 0.91, P < 0.001; diastole: ρ = 0.85, P < 0.001) and EL (systole: ρ = 0.82, P < 0.001; diastole: ρ = 0.89, P < 0.001). Fontan patients with normal EF showed significantly higher vorticity&#95;vol avg systole and EL avg systole , but significantly decreased KE avg diastole , 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. NEW & NOTEWORTHY 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.

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.

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 (-0.42 vs. -0.02 length Z-score per year, P < 0.001), less decrease in N-terminal pro-B-type natriuretic peptide (NT-proBNP) (-0.26 vs. -1.06 2log pg/mL/year, P < 0.01), no decrease in left ventricular internal diastolic dimension (LVIDd; 0.24 vs. -0.60 Boston Z-score per year, P < 0.01), and increase in New York University Pediatric Heart Failure Index (NYU PHFI; 0.49 vs. -1.16 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 two-fold 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., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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

Objective: To assess the atrial and ventricular diastolic function response to dobutamine stress in Fontan patients, and to relate these measurements to exercise capacity and events during the follow-up., Methods: We performed a secondary analysis of a cross-sectional multicentre study of Fontan patients with intra-atrial lateral tunnel (ILT) or extracardiac conduit (ECC) modification. Subjects underwent cardiac MRI during rest and low-dose dobutamine stress, and cardiopulmonary exercise testing. Atrial and diastolic ventricular function parameters were derived from volume-time curves.Medical records were abstracted for a composite end-point of death, listing for transplant, arrhythmia and reintervention. Spearman's r correlation tests and Cox proportional hazards models were used to assess the relation between the dobutamine response for atrial and diastolic ventricular function and outcomes, including exercise capacity., Results: We included 57 patients (26 ECC; 31 ILT) aged 12.8 (IQR (10.3-15.5)) years. During dobutamine stress atrial cyclic volume change increased (3.0 (0.4-5.9) mL/m 2 , p<0.001), as did early (1.9 (-1.6 to 3.6) mL/m 2 , p=0.001) and late emptying volume (2.2 (0.2-4.4) mL/m 2 , p<0.001).Ventricular early filling decreased (-1.6 (-5.7 to 0.7) mL/m 2 ,p=0.046) and ventricular late filling increased (1.0 (-0.4 to 3.4) mL/m 2 ,p<0.001) while stroke volume remained similar.Only for patients with the ECC modification, atrial early emptying volume increase correlated with peak oxygen uptake (ρ=0.66,p=0.002). No other parameter related to exercise capacity.During a median 7.1-year follow-up, 22 patients reached the composite endpoint. No parameter predicted events during the follow-up., Conclusions: Dobutamine stress augmented atrial reservoir and pump function for Fontan patients. Atrial early emptying reserve related to exercise capacity in ECC patients. No other atrial or diastolic ventricular function parameter related to outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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 ( P =0.005) and vWF ( P =0.008) and high levels of DLK-1 ( P =0.041). There was a positive correlation (β=0.33, P =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.

Background: Cardiovascular magnetic resonance (CMR) phase contrast (PC) flow measurements suffer from phase offset errors. Background subtraction based on stationary phantom measurements can most reliably be used to overcome this inaccuracy. Stationary tissue correction is an alternative and does not require additional phantom scanning. The aim of this study was 1) to compare measurements with and without stationary tissue correction to phantom corrected measurements on different GE Healthcare CMR scanners using different software packages and 2) to evaluate the clinical implications of these methods., Methods: CMR PC imaging of both the aortic and pulmonary artery flow was performed in patients on three different 1.5 T CMR scanners (GE Healthcare) using identical scan parameters. Uncorrected, first, second and third order stationary tissue corrected flow measurement were compared to phantom corrected flow measurements, our reference method, using Medis QFlow, Circle cvi42 and MASS software. The optimal (optimized) stationary tissue order was determined per scanner and software program. Velocity offsets, net flow, clinically significant difference (deviation > 10% net flow), and regurgitation severity were assessed., Results: Data from 175 patients (28 (17-38) years) were included, of which 84% had congenital heart disease. First, second and third order and optimized stationary tissue correction did not improve the velocity offsets and net flow measurements. Uncorrected measurements resulted in the least clinically significant differences in net flow compared to phantom corrected data. Optimized stationary tissue correction per scanner and software program resulted in net flow differences (> 10%) in 19% (MASS) and 30% (Circle cvi42) of all measurements compared to 18% (MASS) and 23% (Circle cvi42) with no correction. Compared to phantom correction, regurgitation reclassification was the least common using uncorrected data. One CMR scanner performed worse and significant net flow differences of > 10% were present both with and without stationary tissue correction in more than 30% of all measurements., Conclusion: Phase offset errors had a significant impact on net flow quantification, regurgitation assessment and varied greatly between CMR scanners. Background phase correction using stationary tissue correction worsened accuracy compared to no correction on three GE Healthcare CMR scanners. Therefore, careful assessment of phase offset errors at each individual scanner is essential to determine whether routine use of phantom correction is necessary., Trial Registration: Observational Study.

Aims: The aim of this study was to evaluate the possible value of dobutamine stress cardiac magnetic resonance imaging (CMR) to predict adverse outcome in Tetralogy of Fallot (TOF) patients., Methods and Results: In previous prospective multicentre studies, TOF patients underwent low-dose dobutamine stress CMR (7.5 µg/kg/min). Subsequently, during regular-care patient follow-up, patients were assessed for reaching the composite endpoint (cardiac death, arrhythmia-related hospitalization, or cardioversion/ablation, VO2 max ≤65% of predicted). A normal stress response was defined as a decrease in end-systolic volume (ESV) and increase in ejection fraction. The relative parameter change during stress was calculated as relative parameter change = [(parameterstress - parameterrest)/parameterrest] * 100. The predictive value of dobutamine stress CMR for the composite endpoint was determined using time-to-event analyses (Kaplan-Meier) and Cox proportional hazard analysis. We studied 100 patients [67 (67%) male, median age at baseline CMR 17.8 years (interquartile range 13.5-34.0), age at TOF repair 0.9 years (0.6-2.1)]. After a median follow-up of 8.6 years (6.7-14.1), 10 patients reached the composite endpoint. An abnormal stress response (30% vs. 4.4%, P = 0.021) was more frequently observed in composite endpoint patients. Also in endpoint patients, the relative decrease in right ventricular ESV decreased less during stress compared with the patients without an endpoint (-17 ± 15 vs. -26 ± 13 %, P = 0.045). Multivariable analyses identified an abnormal stress response (hazard ratio 10.4; 95% confidence interval 2.5-43.7; P = 0.001) as predictor for the composite endpoint., Conclusion: An abnormal ventricular response to dobutamine stress is associated with adverse outcome in patients with repaired TOF., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To assess the role of atrial function on exercise capacity and clinical events in Fontan patients., Design: We included 96 Fontan patients from 6 tertiary centers, aged 12.8 (IQR 10.1-15.6) years, who underwent cardiac magnetic resonance imaging and cardiopulmonary exercise testing within 12 months of each other from 2004 to 2017. Intra-atrial lateral tunnel (ILT) and extracardiac conduit (ECC) patients were matched 1:1 with regard to age, gender and dominant ventricle. The pulmonary venous atrium was manually segmented in all phases and slices. Atrial function was assessed by volume-time curves. Furthermore, atrial longitudinal and circumferential feature tracking strain was assessed. We determined the relation between atrial function and exercise capacity, assessed by peak oxygen uptake and VE/VCO 2 slope, and events (mortality, listing for transplant, re-intervention, arrhythmia) during follow-up., Results: Atrial maximal and minimal volumes did not differ between ILT and ECC patients. ECC patients had higher reservoir function (21.1 [16.4-28.0]% vs 18.2 [10.9-22.2]%, p = .03), lower conduit function and lower total circumferential strain (13.8 ± 5.1% vs 18.0 ± 8.7%, p = .01), compared to ILT patients. Only for ECC patients, a better late peak circumferential strain rate predicted better VE/VCO 2 slope. No other parameter of atrial function predicted peak oxygen uptake or VE/VCO 2 slope. During a median follow-up of 6.2 years, 42 patients reached the composite end-point. No atrial function parameters predicted events during follow-up., Conclusions: ECC patients have higher atrial reservoir function and lower conduit function. Atrial function did not predict exercise capacity or events during follow-up., Competing Interests: Conflict of interest All authors declare no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background Adiposity is associated with larger left ventricular mass in children and adults. The role of body fat distribution in these associations is not clear. We examined the associations of body fat distribution and overweight with cardiac measures obtained by cardiac magnetic resonance imaging in school-age children. Methods and Results In a population-based cohort study including 2836 children, 10 years of age, we used anthropometric measures, dual-energy X-ray absorptiometry, and magnetic resonance imaging to collect information on body mass index, lean mass index, fat mass index, and abdominal visceral adipose tissue index. Indexes were standardized by height. Cardiac measures included right and left ventricular end-diastolic volume, left ventricular mass, and mass-to-volume ratio as a marker for concentricity. All body fat measures were positively associated with right and left ventricular end-diastolic volumes and left ventricular mass, with the strongest associations for lean mass index (all P <0.05). Obese children had a 1.12 standard deviation score (95% CI, 0.94-1.30) larger left ventricular mass and a 0.35 standard deviation score (95% CI, 0.14-0.57) higher left ventricular mass-to-volume ratio than normal weight children. Conditional on body mass index, higher lean mass index was associated with higher right and left ventricular end-diastolic volume and left ventricular mass, whereas higher fat mass measures were inversely associated with these cardiac measures (all P <0.05). Conclusions Higher childhood body mass index is associated with a larger right and left ventricular size. This association is influenced by higher lean mass. In childhood, lean mass may be a stronger determinant of heart growth than fat mass. Fat mass may influence cardiac structures at older ages.

Objectives: Our goal was to report the long-term serial follow-up after transatrial-transpulmonary repair of tetralogy of Fallot (TOF) and to describe the influence of the timing of the repair on outcome., Methods: We included all patients with TOF who had undergone transatrial-transpulmonary repair between 1970 and 2012. Records were reviewed for patient demographics, operative details and events during the follow-up period (death, pulmonary valve replacement, cardiac reinterventions and hospitalization/intervention for arrhythmias). In patients with elective early primary repair of TOF after 1990, a subanalysis of the optimal timing of TOF repair was performed., Results: A total of 453 patients were included (63% male patients; 65% had transannular patch); 261 patients underwent primary elective repair after 1990. The median age at TOF repair was 0.7 years (25th-75th percentile 0.3-1.3) and decreased from 1.7 to 0.4 years from before 1990 to after 2000, respectively (P < 0.001). The median follow-up duration after TOF repair was 16.8 years (9.6-24.7). Events developed in 182 (40%) patients. In multivariable analysis, early repair of TOF (<6 months) [hazard ratio (HR) 3.06; P < 0.001] and complications after TOF repair (HR 2.18; P = 0.006) were found to be predictive for an event. In a subanalysis of the primary repair of TOF after 1990, the patients (n = 125) with elective early repair (<6 months) experienced significantly worse event-free survival compared to patients who had elective repair later (n = 136). In multivariable analysis, early repair (HR 3.00; P = 0.001) and postoperative complications (HR 2.12; P = 0.010) were associated with events in electively repaired patients with TOF., Conclusions: Transatrial-transpulmonary repair of TOF before the age of 6 months may be associated with more events during the long-term follow-up period., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

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 without a SE. In both patients groups, 6MWD% remained constant over time. An absolute 1% lower 6MWD% was associated with an 11% higher risk (hazard) of the SE (HR 0.90, 95% CI 0.86-0.95 p < 0.001). Children with DCM who died or underwent heart transplantation had systematically reduced 6MWD%. The performance of all patients was stable over time, so repeated measurement of 6MWT within this time frame had little added value over a single test.

Objectives: Early life is critical for cardiac development. We examined the associations of longitudinal fetal and childhood growth patterns with childhood right and left ventricular structures measured by cardiac magnetic resonance imaging., Methods: In a population-based prospective cohort study among 2827 children, we measured growth at 20 and 30 weeks of pregnancy, at birth, 0.5, 1, 2, 6 and 10 years. At 10 years, we measured right ventricular end-diastolic volume, left ventricular end-diastolic volume, left ventricular mass and left ventricular mass-to-volume ratio by cardiac magnetic resonance imaging., Results: Small size for gestational age at birth was associated with smaller right and left ventricular end-diastolic volume relative to current body surface area, but with larger left ventricular mass-to-volume ratio ( P  < 0.05). Children in the upper 25% of right and left ventricular end-diastolic volume and left ventricular mass at age 10 years were larger at birth and became taller and leaner in childhood ( P  < 0.05). In contrast, children in the lower 25% of right and left ventricular end-diastolic volume and left ventricular mass were smaller at birth and became shorter and heavier in childhood ( P  < 0.05). Both fetal and childhood growth were independently of each other associated with childhood right and left ventricular end-diastolic volume and left ventricular mass., Conclusion: Children who are larger at birth and grow taller and leaner in childhood have larger hearts relative to body surface area. Small size at birth children, who grow shorter and heavier in childhood, have relatively smaller hearts with larger left ventricular mass-to-volume ratio. Both fetal and childhood growth are important for the development of cardiac dimensions.

Whilst stenosis of systemic and pulmonary arteries in Williams syndrome is frequently described, aneurysm formation is uncommon. We provide the first description of a Williams patient with development of an aneurysm of the arterial duct. This aneurysm developed concomitantly with supravalvar aortic, and peripheral pulmonary stenosis. The duct was closed interventionally to reduce the risk of rupture.

Objective: Children with congenital heart disease and their families are at risk of psychosocial problems. Emotional and behavioural problems, impaired school functioning, and reduced exercise capacity often occur. To prevent and decrease these problems, we modified and extended the previously established Congenital Heart Disease Intervention Program (CHIP)-School, thereby creating CHIP-Family. CHIP-Family is the first psychosocial intervention with a module for children with congenital heart disease. Through a randomised controlled trial, we examined the effectiveness of CHIP-Family., Methods: Ninety-three children with congenital heart disease (age M = 5.34 years, SD = 1.27) were randomised to CHIP-Family (n = 49) or care as usual (no psychosocial care; n = 44). CHIP-Family consisted of a 1-day group workshop for parents, children, and siblings and an individual follow-up session for parents. CHIP-Family was delivered by psychologists, paediatric cardiologists, and physiotherapists. At baseline and 6-month follow-up, mothers, fathers, teachers, and the child completed questionnaires to assess psychosocial problems, school functioning, and sports enjoyment. Moreover, at 6-month follow-up, parents completed program satisfaction assessments., Results: Although small improvements in child outcomes were observed in the CHIP-Family group, no statistically significant differences were found between outcomes of the CHIP-Family and care-as-usual group. Mean parent satisfaction ratings ranged from 7.4 to 8.1 (range 0-10)., Conclusions: CHIP-Family yielded high program acceptability ratings. However, compared to care as usual, CHIP-Family did not find the same extent of statistically significant outcomes as CHIP-School. Replication of promising psychological interventions, and examination of when different outcomes are found, is recommended for refining interventions in the future., Trial Registry: Dutch Trial Registry number NTR6063, https://www.trialregister.nl/trial/5780.

Objectives: Our goals were to compare the outcome of the intra-atrial lateral tunnel (ILT) and the extracardiac conduit (ECC) techniques for staged total cavopulmonary connection (TCPC) and to compare the current modifications of the TCPC technique, i.e. the prosthetic ILT technique with the current ECC technique with a ≥18-mm conduit., Methods: We included patients who had undergone a staged TCPC between 1988 and 2008. Records were reviewed for patient demographics, operative details and events during follow-up (death, surgical and catheter-based reinterventions and arrhythmias)., Results: Of the 208 patients included, 103 had the ILT (51 baffle, 52 prosthetic) technique and 105 had the ECC technique. Median follow-up duration was 13.2 years (interquartile range 9.5-16.3). At 15 years after the TCPC, the overall survival rate was comparable (81% ILT vs 89% ECC; P = 0.12). Freedom from late surgical and catheter-based reintervention was higher for patients who had ILT than for those who had ECC (63% vs 44%; P = 0.016). However, freedom from late arrhythmia was lower for patients who had ILT than for those who had ECC (71% vs 85%, P = 0.034). In a subgroup of patients who had the current TCPC technique, when we compared the use of a prosthetic ILT with ≥18-mm ECC, we found no differences in freedom from late arrhythmias (82% vs 86%, P = 0.64) or in freedom from late reinterventions (70% vs 52%, P = 0.14)., Conclusions: A comparison between the updated prosthetic ILT and current ≥18-mm ECC techniques revealed no differences in late arrhythmia-free survival or late reintervention-free survival. Overall, outcomes after the staged TCPC were relatively good and reinterventions occurred more frequently in the ECC group, whereas late arrhythmias were more common in the ILT group., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Tetralogy of Fallot (ToF) is the most common type of cyanotic congenital heart disease. Since the first surgical repair in 1954, treatment has continuously improved. The treatment strategies currently used in the treatment of ToF result in excellent long-term survival (30 year survival ranges from 68.5% to 90.5%). However, residual problems such as right ventricular outflow tract obstruction, pulmonary regurgitation, and (ventricular) arrhythmia are common and often require re-interventions. Right ventricular dysfunction can be seen following longstanding pulmonary regurgitation and/or stenosis. Performing pulmonary valve replacement or relief of pulmonary stenosis before irreversible right ventricular dysfunction occurs is important, but determining the optimal timing of pulmonary valve replacement is challenging for several reasons. The biological mechanisms underlying dysfunction of the right ventricle as seen in longstanding pulmonary regurgitation are poorly understood. Different methods of assessing the right ventricle are used to predict impending dysfunction. The atrioventricular, ventriculo-arterial and interventricular interactions of the right ventricle play an important role in right ventricle performance, but are not fully elucidated. In this review we present a brief overview of the history of ToF, describe the treatment strategies currently used, and outline the long-term survival, residual lesions, and re-interventions following repair. We discuss important remaining challenges and present the current state of the art regarding these challenges., Competing Interests: No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.

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.

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&#95;vol avg cycle , KE avg cycle, EL avg cycle ). The relation to maximum oxygen uptake (VO 2 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 avg cycle : 1.8 ± 0.5 vs 3.3 ± 0.9 mJ, P < 0.001), a significant 108 ± 49% increase in EL (EL avg cycle : 0.9 ± 0.4 vs 1.9 ± 0.9 mW, P < 0.001) and a significant 27 ± 19% increase in vorticity (vorticity&#95;vol avg cycle : 3441 ± 899 vs 4394 ± 1322 mL/s, P = 0.002). All rest-stress differences (%) were negatively correlated to VO 2 max (KE avg cycle : r = - 0.83, P = 0.003; EL avg cycle : r = - 0.80, P = 0.006; vorticity&#95;vol avg cycle : 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 2 max.

Fontan failure remains a significant problem, especially in patients with an atriopulmonary Fontan. Fontan baffle volume change during the cardiac cycle (Fontan baffle stroke volume) may affect outcomes in Fontan circulation. Assuming that increased Fontan baffle stroke volume is associated with increased energy loss in the baffle, we hypothesized that higher baffle stroke volume is associated with worse exercise capacity and increased incidence of Fontan failure. Patients from 6 centers with an atriopulmonary or lateral tunnel Fontan operation were included if they had a cardiac magnetic resonance (CMR) study and an adequate cardiopulmonary exercise test. Fontan baffle stroke volume was defined as the difference between maximum and minimum Fontan baffle volumes. Fontan failure was defined as death, listing for transplantation, heart failure symptoms requiring medications, or peak VO 2 below 16 ml/kg/min. The study group consisted of 107 patients (median age 19 years, interquartile range, 14 to 29 years). Most patients (84%) had lateral tunnel procedure. During a median follow-up period of 6.8 [interquartile range: 3.2 to 8.8] years after the CMR, 25 (23%) patients had Fontan failure (7 deaths, 3 listed for transplantation, and 15 with heart failure symptoms). Predictors of Fontan failure on multivariable analysis were ventricular tachycardia, protein losing enteropathy, and additionally in atriopulmonary Fontan only, larger Fontan baffle stroke volume. Predictors of lower peak VO 2 on multivariable analysis were older age at CMR and additionally in atriopulmonary Fontan only, larger Fontan baffle stroke volume. In conclusion, larger Fontan baffle stroke volume was independently associated with lower peak VO 2 and Fontan failure in atriopulmonary Fontan., (Copyright © 2019 Elsevier Inc. All rights reserved.)