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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.)

Tricuspid valvectomy is a rare surgical intervention, and knowledge regarding long-term outcome in children is lacking. We report a favourable outcome 11 years after tricuspid valvectomy in early infancy without subsequent surgery or other cardiac interventions. Specific criteria for timing of re-intervention are lacking. Application of adult tricuspid and pulmonary regurgitation recommendations is helpful but has limitations.

Aims: To non-invasively assess intraventricular viscous energy loss (EL) and proportionality to kinetic energy (KE) in Fontan patients using 4D flow magnetic resonance imaging (MRI) and compare to healthy controls., Methods and Results: Thirty Fontan patients and 15 controls underwent 4D flow MRI. Ventricular EL was computed and normalized by end-diastolic volume (EDV). EL over the cardiac cycle (ELcycle) relative to the average kinetic energy (KEcycle) was quantified using a dimensionless index, ELindex (ELcycle/KEcycle). EL was significantly elevated in Fontan patients compared to controls (ELcycle/EDV: 3.7 vs. 2.6 J/m3, P = 0.001). Fontan patients with inflow of blood entering a ventricle, which leaves that ventricle through a ventricular septal defect to the aorta, defined as discordant inflow-to-outflow showed significantly higher EL compared to patients with inflow of blood into the same ventricle from which the blood is ejected into the aorta, defined as concordant inflow-to-outflow (ELcycle/EDV: 6.8 vs. 3.2 J/m3, P = 0.001). EL was not significantly different in Fontan patients with a systemic left vs. a systemic right ventricle (ELcycle/EDV: 3.5 vs. 3.6 J/m3, P = 0.91). ELindex was significantly elevated in Fontan patients compared to controls (ELindex: 0.4 vs. 0.2, P < 0.001). Highest ELindex was found in Fontan patients with discordant inflow-to-outflow compared to concordant inflow-to-outflow (0.5 vs. 0.3, P = 0.01)., Conclusion: Fontan patients show disproportionate intraventricular EL relative to KE. Intraventricular EL is elevated in these patients compared to healthy controls, and highest EL is found in patients with discordant inflow-to-outflow., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: Myocardial deformation by speckle tracking echocardiography provides additional information on left ventricular function. Values of myocardial deformation (strain and strain rate) depend on the type of ultrasound machine and software that is used. Normative values for QLAB (Philips) are scarce, especially for children. It is important to evaluate the influence of age and body size on myocardial deformation parameters, since anthropometrics strongly influence many standard echocardiographic parameters. The aim of this study was to provide comprehensive normal values for myocardial deformation of the left ventricle using a Philips platform and to evaluate the association with anthropometric and standard echocardiographic parameters., Methods: Healthy children between 1 and 18 years of age were prospectively examined using a standard echocardiographic protocol. Short-axis and apical four-chamber, two-chamber, and three-chamber views were used to measure peak systolic circumferential and longitudinal strain and systolic and early diastolic strain rate of the left ventricle using dedicated software., Results: A total of 103 children were included with a mean age of 10.8 and inter-quartile range 7.3-14.3 years. Global circumferential strain values (±SD) were -24.2±3.5% at basal, -25.8±3.5% at papillary muscle, and -31.9±6.2% at apex levels. Global left ventricular longitudinal strain values were -20.6±2.6% in apical four-chamber view, -20.9±2.7% in apical two-chamber, and -21.0 ±2.7% in apical three-chamber. Age was associated with longitudinal strain, longitudinal systolic and early diastolic strain rate, but not with circumferential strain., Conclusions: Normal values for left ventricular deformation parameters in children are obtained using a Philips platform. Age partly explains normal variation of strain and strain rate.

Premature birth and bronchopulmonary dysplasia (BPD) are risk factors for the development of echocardiographic signs of pulmonary hypertension (PH) and are associated with changes in cardiac structure and function. It is unclear whether this association persists beyond early infancy. The aims of this study are to prospectively investigate the prevalence of PH in children with severe BPD and to investigate the effect of BPD and PH on myocardial structure and function at six months corrected age. Preterm infants (gestational age ≤ 32 weeks) with severe BPD were included. Echocardiography was used to define PH and to measure speckle tracking derived longitudinal and circumferential strain of the left ventricle (LV) and right ventricle (RV). Sixty-nine infants with a median (interquartile range [IQR]) gestational age of 25.6 (24.9-26.4) weeks and a median birthweight of 770 (645-945) gram were included. Eight (12%) infants had signs of PH at six months corrected age. RV fractional area change was lower in infants with severe BPD and PH at six months compared to infants without PH (35% ± 9% vs. 43% ± 9%, P = 0.03). RV mean longitudinal systolic strain was lower in infants with severe BPD and PH compared to infants without PH (17.6% [-19.5%/-16.1%] vs. -20.9% [-25.9%/-17.9%], P = 0.04). RV size and LV longitudinal and circumferential strain in children with BPD with or without PH were similar. Signs of PH were found in 12% of infants with severe BPD at six months corrected age and the presence of PH is associated with reduced RV systolic function.

Background: To assess the current state of patient information and decision-making in congenital aortic and pulmonary valve disease, we conducted a survey among patients, parents and physicians., Methods: A questionnaire was sent by ground mail to 157 adults and 32 parents of children who previously underwent surgery for congenital aortic or pulmonary valve disease at 0-40 years of age between January 2005 and February 2014 at the Erasmus University Medical Center and to all paediatric and adult congenital cardiologists and congenital cardiac surgeons in the Netherlands (n=88)., Results: 73 patients/parents (39% response rate, 62 adult patients, 11 parents of paediatric patients) and 35 physicians (40% response rate) responded. Median patient age at the time of surgery was 25.7 years. Basic disease-specific knowledge was adequate in 42% of patients/parents and numeracy was sufficient in 47%. Patients/parents reported that they rely heavily on their physicians for information and often experience difficulty in finding reliable information elsewhere. They lack information on psychosocial aspects of disease (29% of respondents) and risks and benefits of treatment options (26%). They feel less involved in decision-making than they would prefer to be (p=0.014). Decisional conflict at the time of surgery was experienced by 31% of patients/parents. If they had to do it again, 72% of patients/parents would want the same treatment. Quality of life is often impaired due to various valve-related anxieties and lifestyle changes. Physicians reported that they are unable to fully inform and sufficiently involve patients, due to limited patient/parent knowledge and understanding (56%) and limited time during consultations (32%). Patients/parents (98%) and physicians (97%) agree that they should have shared roles in decision-making., Conclusion: The substantial shortcomings in our current practice of patient information and decision-making underline the need for innovative solutions, such as careful implementation of patient information tools and shared decision-making in the care path., Competing Interests: Competing interests: None declared.

Background: Forecasting the prognosis of a child when diagnosed with Ebstein's anomaly is difficult. We, therefore, studied which factors at the time of diagnosis are associated with death during childhood., Methods: All consecutive patients (0-18 years) diagnosed with Ebstein's anomaly in the Netherlands between 1980 and 2014 were included. Survival curves were obtained using the Kaplan-Meier method. By using the Cox proportional hazard model, we analysed the factors (at diagnosis) that were associated with death., Results: We included 176 patients. Thirty-one patients (18%) died before the age of 18 years. The 1-year survival was 84% and remained stable at 82% from 35 months after diagnosis and onwards. Modified Ross Heart Failure Class 4 at the time of diagnosis was the most important risk factor for death during childhood (HR 12.5, 95% CI 4.4 to 35.9). Furthermore, diagnosis in the neonatal period (HR 4.2, 95% CI 1.5 to 12.0), severe tricuspid valve regurgitation (HR 2.4, 95% CI 1.2 to 5.0), severe right ventricular outflow tract obstruction (HR 3.7, 95% CI 1.8 to 7.7) and a patent ductus arteriosus (HR 2.8, 95% CI 1.3 to 6.0) at the time of diagnosis were univariately associated with death. Multivariable analysis showed that presentation with Heart Failure Class 4 and a ventricular septal defect is the strongest predictor of death in childhood and adolescence., Conclusion: Patients with Ebstein's anomaly presenting with Heart Failure Class 4 and a ventricular septal defect have a high risk of death during childhood., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

In patients with a functionally univentricular heart, the Fontan strategy achieves separation of the systemic and pulmonary circulation and reduction of ventricular volume overload. Contemporary modifications of surgical techniques have significantly improved survival. However, the resulting Fontan physiology is associated with high morbidity. In this review, we discuss the state of the art of the Fontan strategy by assessing survival and risk factors for mortality. Complications of the Fontan circulation, such as cardiac arrhythmia, thromboembolism, and protein-losing enteropathy, are discussed. Common surgical and catheter-based interventions following Fontan completion are outlined. We describe functional status measurements such as quality of life and developmental outcomes in the contemporary Fontan patient. The current role of drug therapy in the Fontan patient is explored. Furthermore, we assess the current use and outcomes of mechanical circulatory support in the Fontan circulation and novel surgical innovations. Despite large improvements in outcomes for contemporary Fontan patients, a large burden of disease exists in this patient population. Continued efforts to improve outcomes are warranted. Several remaining challenges in the Fontan field are outlined., Competing Interests: No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.

Objective: Follow-up of right ventricular performance is important for patients with congenital heart disease. Cardiac magnetic resonance imaging is optimal for this purpose. However, observer-dependency of manual analysis of right ventricular volumes limit its use. Knowledge-based reconstruction is a new semiautomatic analysis tool that uses a database including knowledge of right ventricular shape in various congenital heart diseases. We evaluated whether knowledge-based reconstruction is a good alternative for conventional analysis., Design: To assess the inter- and intra-observer variability and agreement of knowledge-based versus conventional analysis of magnetic resonance right ventricular volumes, analysis was done by two observers in a mixed group of 22 patients with congenital heart disease affecting right ventricular loading conditions (dextro-transposition of the great arteries and right ventricle to pulmonary artery conduit) and a group of 17 healthy children. We used Bland-Altman analysis and coefficient of variation., Results: Comparison between the conventional method and the knowledge-based method showed a systematically higher volume for the latter group. We found an overestimation for end-diastolic volume (bias -40 ± 24 mL, r = .956), end-systolic volume (bias -34 ± 24 mL, r = .943), stroke volume (bias -6 ± 17 mL, r = .735) and an underestimation of ejection fraction (bias 7 ± 7%, r = .671) by knowledge-based reconstruction. The intra-observer variability of knowledge-based reconstruction varied with a coefficient of variation of 9% for end-diastolic volume and 22% for stroke volume. The same trend was noted for inter-observer variability., Conclusion: A systematic difference (overestimation) was noted for right ventricular size as assessed with knowledge-based reconstruction compared with conventional methods for analysis. Observer variability for the new method was comparable to what has been reported for the right ventricle in children and congenital heart disease with conventional analysis., (© 2017 Wiley Periodicals, Inc.)

Background: Dilated cardiomyopathy in children causes heart failure and has a poor prognosis. Health-related quality of life in this patient group is unknown. Moreover, results may provide detailed information of parents' sense of their child's functioning. We hypothesised that health-related quality of life, as rated by parents, and the paediatric heart failure score, as assessed by physicians, have both predictive value on outcome. Methods and results In this prospective study, health-related quality of life was assessed by parent reports: the Infant Toddler Quality of Life questionnaire (0-4 years) or Child Health Questionnaire-Parent Form 50 (4-18 years) at 3-6-month intervals. We included 90 children (median age 3.8 years, interquartile range (IQR) 0.9-12.3) whose parents completed 515 questionnaires. At the same visit, physicians completed the New York University Pediatric Heart Failure Index. Compared with Dutch normative data, quality of life was severely impaired at diagnosis (0-4 years: 7/10 subscales and 4-18 years: 8/11 subscales) and ⩾1 year after diagnosis (3/10 and 6/11 subscales). Older children were more impaired (p<0.05). After a median follow-up of 3 years (IQR 2-4), 15 patients underwent transplantation. Using multivariable time-dependent Cox regression, "physical functioning" subscale and the Heart Failure Index were independently predictive of the risk of death and heart transplantation (hazard ratio 1.24 per 10% decrease of predicted, 95% confidence interval (CI) 1.06-1.47 and hazard ratio 1.38 per unit, 95% CI 1.19-1.61, respectively)., Conclusion: Physical impairment rated by parents and heart failure severity assessed by physicians independently predicted the risk of death or heart transplantation in children with dilated cardiomyopathy.

Objectives: This study aimed to evaluate the predicting value of quantitative and qualitative dyssynchrony parameters as assessed by two-dimensional speckle tracking echocardiography (STE) on outcome in children with dilated cardiomyopathy (DCM). Furthermore, the reproducibility of these parameters was investigated., Background: In previous studies in adults with heart failure, several dyssynchrony parameters have been shown to be a valuable predictor of clinical outcome., Methods: This multicenter, prospective study included 75 children with DCM and 75 healthy age-matched controls. Using STE, quantitative (time to global peak strain and parameters describing intraventricular time differences) and qualitative dyssynchrony parameters (pattern analysis) of the apical four-chamber, three-chamber, two-chamber views, and the short axis of the left ventricle were assessed. Cox regression was used to identify risk factors for the primary endpoints of death or heart transplantation. Inter-observer and intra-observer variability were described., Results: During a median of 21 months follow-up, 10 patients (13%) reached an endpoint. Although quantitative dyssynchrony measures were higher in patients as compared to controls, the inter-observer and intra-observer variability were high. Pattern analysis showed mainly reduced strain, instead of dyssynchronous patterns., Conclusions: In this study, quantitative dyssynchrony parameters were not reproducible, precluding their use in children. Qualitative pattern analysis showed predominantly reduced strain, suggesting that in children with DCM dyssynchrony may be a minor problem., (© 2017, Wiley Periodicals, Inc.)

Aim: Congenital heart diseases are the most common birth defects worldwide and leading cause of infant mortality. The perimembranous ventricular septal defect is most prevalent. Epigenetics may provide an underlying mechanism of the gene-environment interactions involved., Materials & Methods: We examined epigenome-wide DNA methylation using the Illumina HumanMethylation450 BeadChip in 84 case children and 196 control children., Results: We identified differential methylation of a CpG locus (cg17001566) within the PRDM16 gene after Bonferroni correction (p = 9.17 × 10 -8 ). This was validated by bisulfite pyrosequencing. PRDM16 functions as a repressor of TGF-β signaling controlling tissue morphogenesis crucial during cardiogenesis. At 15% false-discovery rate, we identified seven additional CpG loci., Conclusion: These findings provide novel insights in the pathogenesis of perimembranous ventricular septal defect, which is of interest for future prediction and prevention.

Objective: The aim of this study was to investigate the psychosocial needs of both parents of children with CHD (aged 0-18 years) and patients themselves (aged 8-18 years) in the week before cardiac surgery or a catheter intervention. Patients Eligible participants included all consecutive patients (0-18 years) scheduled to undergo cardiac surgery or a catheter intervention in our hospital between March, 2012 and July, 2013. Psychosocial needs were assessed using a disease-specific questionnaire designed for this study, consisting of a 83-item parent version and a 59-item child version (for children ⩾8 years), each covering five domains: physical/medical, emotional, social, educational/occupational, and health behaviour; two items assessed from whom and in what format psychosocial care was preferred. Quality of life was also assessed. Interventions If parents/patients reported a need for psychosocial care, referral to adequate mental health-care professionals was arranged., Results: More than 40% of participating parents and >50% of participating children reported a need for psychosocial care on each of the five domains. Needs for psychosocial care for parents themselves were highest for those with children aged 0-12 years. Parents and patients report clear preferences when asked from whom and in what format they would like to receive psychosocial care. Quality of life was relatively high for both parents and patients. Psychosocial care interventions in our hospital increased significantly after the implementation of this study., Conclusions: Results show that psychosocial care is rated as (very) important by both parents and children during an extremely stressful period of their life.

Objective: To provide prospective information on long-term outcome after surgical correction of valvular pulmonary stenosis (PS)., Methods: Fifty-three consecutive patients operated for PS during childhood between 1968 and 1980 in one centre are followed longitudinally for 37±3.4 years, including extensive in-hospital examination every 10 years., Results: Survival information was available in 100% of the original 53 patients. Cumulative survival was 94% at 20 years and 91% at 40 years. Excluding perioperative mortality (<30 days), survival was 94% at 40 years. Of 46 eligible survivors, 29 participated in the in-hospital examination and 15 gave permission to use their hospital records (96% participation). Cumulative event-free survival was 68% after 40 years: 25% needed a reintervention, 12% underwent pacemaker implantation and 9% had supraventricular arrhythmias. Early reinterventions were mainly for residual PS, late reinterventions for pulmonary regurgitation. Subjective health status was good. Exercise capacity was normal in 74% (median 96 (82-107)% of expected workload). Right ventricular and left ventricular (LV) dysfunction was found in 13% and 41%, respectively. The use of a transannular patch and younger age at surgery were predictive for late events (HR 3.02 (95% CI 1.09 to 8.37) and HR 0.81/year (95% CI 0.66 to 0.98), respectively). Use of inflow occlusion compared with cardiopulmonary bypass showed a trend towards more reinterventions (HR 3.19 (95% CI 0.97 to 10.47))., Conclusions: Survival up to 40 years after successful PS repair is nearly normal. Subjective health status is good and there is a low incidence of arrhythmias. Reinterventions, however, are necessary in one-quarter and 40 years postoperatively several patients show LV dysfunction., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Children and adolescents with a congenital heart defect (ConHD) frequently undergo painful or frightening medical procedures and hospitalizations. They often need multiple invasive procedures at a very young age and require regular checkups during their entire life. From other pediatric populations, it is known that these kinds of experiences can result in acute stress reactions and even in post-traumatic stress disorder (PTSD) in the long-term. PTSD and also subthreshold PTSD can lead to serious (psychosocial) impairment. However, limited information is available about PTSD in children with ConHD. Therefore, the aim of this review is to provide a summary of the current literature on post-traumatic stress (PTS) in children and adolescents with ConHD describing the prevalence of PTSD and its predictors/correlates. This review indicates that a range of 12-31% of children undergoing cardiac surgery develop PTSD. A range of 12-14% shows elevated post-traumatic stress symptoms (PTSS). These findings are comparable to those of hospitalized children without ConHD. Noteworthy, most studies used varying self-report questionnaires to measure PTSD and only one study used a semistructured interview. Although all studies point in the same direction of elevated PTSD and PTSS, systematic research is necessary to be able to draw firm conclusions. At present, as far as we know, in most clinics treating patients with ConHD, there is no regular screening for PTS in children with ConHD. In the reviewed literature, there is strong consensus that screening for PTSS and (preventive) psychological care for children and adolescents with ConHD is urgently needed.

Children and adolescents operated upon for congenital heart disease may show reduced exercise capacity and physical activity, associated with lowered quality of life. This review presents intervention studies on the influence of an exercise program on quality of life and psychosocial functioning in children with severe congenital heart disease. Participation in an exercise program among young people with complex congenital heart disease seemed to have positive effects on quality of life and passive leisure time spent. However, more effects of the exercise programs may have been expected. For future research it is important to critically evaluate the content of the exercise programs.

Background: The objective assessment of global and regional cardiac function in children has shown to be clinically relevant but is challenging to conduct. Cardiovascular magnetic resonance (CMR) has emerged as a valuable diagnostic modality especially in patients with cardiomyopathy or congenital heart disease. However, data on the normal cardiac deformation in children assessed by CMR is lacking at present. Thus, the aim of this study was to provide reference values for cardiac strain and strain rate in children and adolescents derived from CMR feature tracking (FT) measurements., Methods: In this binational study, eighty children and adolescents (age 0.4-18.0 years, 41 male, 39 female) free from cardiac diseases from two centers underwent CMR in 1.5 T whole-body scanners in supine position. Global peak radial, circumferential and longitudinal systolic strains as well as the corresponding early peak diastolic strain rates were assessed applying FT on short axis as well as 3- and 4-chamber views of standard cine steady-state free precession images., Results: The difference between genders yielded no significance for all assessed strains. Yet, all strains showed a significant parabolic relation to age and an even stronger one to body surface area (BSA). Therefore, BSA-specific reference values were determined using a polynomial regression model. The apical cardiac segments featured significant higher peak circumferential but lower peak radial systolic strains than the midventricular and basal segments (all p < 0.001)., Conclusions: The assessment of cardiac deformation by CMR-FT is feasible in children. This is the first CMR study providing specific reference values for FT-derived strain and strain rate in the pediatric age range.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an important predictor of outcome in adults with heart failure. In children with heart failure secondary to dilated cardiomyopathy (DC) markers that reliably predict disease progression and outcome during follow-up are scarce. We investigated whether serial NT-proBNP measurements were predictive for outcome in children with DC. All available NT-proBNP measurements in children with DC were analyzed. Linear mixed-effect models and Cox regression were used to analyze the predictive value of NT-proBNP on the end point of cardiac death (death, heart transplantation, or mechanical circulatory support). During 7 years, 115 patients were included. At diagnosis, median NT-proBNP was high and not predictive for outcome. At any time during follow-up, a twofold higher NT-proBNP resulted in a 2.9 times higher risk in the first year (p <0.001) and a 1.8 times higher risk thereafter (p <0.001). Furthermore, at any time, the slope of log10(NT-proBNP) was significantly predictive for the risk of an end point (0 to 30 days hazard ratio [HR] 3.5, >30 days HR 2.9; >1 year HR 6.4). In patients with idiopathic DC (IDC) at 30 days after diagnosis, NT-proBNP ≥7,990 pg/ml showed a 1- and 2-year event-free survival of 79% and 71% and >1 year after diagnosis NT-proBNP ≥924 pg/ml showed a 2- and 5-year event-free survival of 50% and 40%, whereas below both thresholds event-free survival was 100%. In non-IDC, these thresholds were not predictive for outcome. In conclusion, NT-proBNP at any time during follow-up and its change over time were significantly predictive for the risk of cardiac death in children with DC. In children with IDC >1 year after diagnosis, NT-proBNP >924 pg/ml identified a subgroup with a poor outcome., (Copyright © 2016. Published by Elsevier Inc.)

Objective: Low birth weight is associated with cardiovascular disease. We examined the effects of fetal and infant growth patterns on cardiovascular outcomes in children., Methods: In a population-based prospective cohort study among 6239 children, we estimated fetal-femur length and weight by 20 and 30 weeks ultrasound, and child length and weight at birth, 0.5, 1, 2 and 6 years. We measured blood pressure (BP), carotid-femoral pulse wave velocity, aortic root diameter, left ventricular mass and fractional shortening at 6 years. We used regression analyses to identify longitudinal growth patterns associated with height-standardized vascular outcomes and body-surface-area-standardized cardiac outcomes., Results: Younger gestational age and lower birth weight were associated with higher BP, smaller aortic root diameter and lower left ventricular mass in childhood (all P values <0.05). Children with decelerated or normal fetal growth followed by accelerated infant growth had higher BP, whereas those with decelerated growth during both fetal life and infancy had a relatively larger left ventricular mass. Longitudinal growth analyses showed that children with increased BP tended to be smaller during third trimester of fetal life, but of normal size during infancy, than children with normal BP. Children with increased aortic root diameter or left ventricular mass tended to be larger during fetal life, but of similar size during infancy., Conclusion: Specific fetal and infant growth patterns are associated with different cardiovascular outcomes in children. Further studies are needed to identify the underlying mechanisms and the long-term cardiovascular consequences.

Background: The Fontan circulation is the optimal treatment for patients with univentricular hearts. These patients are at high risk of circulatory failure. There is no consensus on the optimal drug treatment for the prevention of failure of the Fontan circulation. The aim of this systematic review was to provide an overview of evidence for drug therapy used in the prevention of Fontan circulatory failure., Methods: We searched the Embase database for articles that reported drug therapy in Fontan patients. Studies published between 1997 and 2014 were included if efficacy or safety of medication was assessed, drug therapy aimed to prevent or treat failure of the Fontan circulation, and if the full text was available. Case reports were excluded., Results: A total of nine studies were included with a total of 267 Fontan patients; four studies evaluated the medication sildenafil, one iloprost, three bosentan, and one enalapril. Among all, two sildenafil studies reported improvement in exercise capacity, one in exercise haemodynamics, and one in ventricular performance. In the largest study of bosentan, an increase in exercise capacity was found. Enalapril did not result in improvements., Conclusion: The studies analysed in this review suggest that bosentan, sildenafil, and iloprost may improve exercise capacity at the short term. Given the limitations of the studies, more, larger, placebo-controlled studies with longer follow-up periods are needed to better understand which drug therapies are effective in the prevention of failure of the Fontan circulation.

Background: Oxygen uptake efficiency (OUE), the relation between oxygen uptake (VO2) and minute ventilation (VE), differs between healthy children and children with heart disease. This study aimed to investigate the normal response profiles of OUE during a progressive cardiopulmonary exercise test., Design: Cross-sectional., Methods: Healthy children between eight and 19 years of age (114 boys and 100 girls, mean ± SD age 12.7 ± 2.8 years) performed a maximal cardiopulmonary exercise test. Peak VO2 (VO2peak), ventilatory threshold and peak VE were determined. OUE was determined by the OUE plateau (OUEP), OUE at the ventilatory threshold (OUE@VT) and OUE slope (OUES)., Results: OUEP (42.4 ± 4.6) and OUE@VT (41.9 ± 4.7) were similar and less variable than OUES (2138 ± 703). OUEP correlated strongly with OUE@VT (r = 0.974); however, OUEP was weak-to-moderately correlated with VO2peak (r = 0.646), the ventilatory threshold (r = 0.548) and OUES (r = 0.589). OUES correlated strongly with VO2peak (r = 0.948) and the ventilatory threshold (r = 0.856). Reference centiles for OUEP show an almost linear increase from about 37 in eight-year olds to about 47 in 18-year olds, with no sex-difference. OUES increased from about 1400 in eight-year-old boys to approximately 3500 in 18-year-old boys. OUES increased from roughly 1250 in eight-year-old girls to about 2650 in 18-year-old girls., Conclusions: This study provides sex- and age-related normative values for both OUEP and OUES, which facilitates the interpretation of OUE in children. OUEP and OUES are objective and non-invasive cardiopulmonary exercise test parameters which do not require a maximal effort and might be indicative of cardiorespiratory function during exercise., (© The European Society of Cardiology 2015.)

Despite successful aortic coarctation (CoA) repair, systemic hypertension often recurs which may influence left ventricular (LV) function. We aimed to detect early LV dysfunction using LV global longitudinal strain (GLS) in adults with repaired CoA, and to identify associations with patient and echocardiographic characteristics. In this cross-sectional study, patients with repaired CoA and healthy controls were recruited prospectively. All subjects underwent echocardiography, ECG and blood sampling within 1 day. With speckle-tracking echocardiography, we assessed LV GLS on the apical four-, three- and two-chamber views. We included 150 subjects: 75 patients (57 % male, age 33.4 ± 12.8 years, age at repair 2.5 [IQR: 0.1-11.1] years) and 75 healthy controls of similar sex and age. LV GLS was lower in patients than in controls (-17.1 ± 2.3 vs. -20.2 ± 1.6 %, P < 0.001). Eighty percent of the patients had a normal LV ejection fraction, but GLS was still lower than in controls (P < 0.001). In patients, GLS correlated with systolic and diastolic blood pressure (r = 0.32, P = 0.009; r = 0.31, P = 0.009), QRS duration (r = 0.34, P = 0.005), left atrial dimension (r = 0.27, P = 0.029), LV mass (r = 0.30, P = 0.014) and LV ejection fraction (r = -0.48, P < 0.001). Patients with either associated cardiac lesions, multiple cardiac interventions or aortic valve replacement had lower GLS than patients without. Although the majority of adults with repaired CoA seem to have a normal systolic LV function, LV GLS was decreased. Higher blood pressure, associated cardiac lesions, and larger left atrial dimension are related with lower GLS. Therefore, LV GLS may be used as objective criterion for early detection of ventricular dysfunction.

Purpose: It is important to identify those children with a Fontan circulation who are at risk for impaired health-related quality of life. We aimed to determine the predictive value of functional health status - medical history and present medical status - on both physical and psychosocial domains of health-related quality of life, as reported by patients themselves and their parents., Methods: We carried out a prospective cross-sectional multi-centre study in Fontan patients aged between 8 and 15, who had undergone staged completion of total cavopulmonary connection according to a current technique before the age of 7 years. Functional health status was assessed as medical history - that is, age at Fontan, type of Fontan, ventricular dominance, and number of cardiac surgical procedures - and present medical status - assessed with magnetic resonance imaging, exercise testing, and rhythm assessment. Health-related quality of life was assessed with The TNO/AZL Child Questionnaire Child Form and Parent Form., Results: In multivariate prediction models, several medical history variables, such as more operations post-Fontan completion, lower age at Fontan completion, and dominant right ventricle, and present medical status variables, such as smaller end-diastolic volume, a higher score for ventilatory efficiency, and the presence of sinus node dysfunction, predicted worse outcomes on several parent-reported and self-reported physical as well as psychosocial health-related quality of life domains., Conclusions: Medical history and worse present medical status not only predicted worse physical parent-reported and self-reported health-related quality of life but also worse psychosocial health-related quality of life and subjective cognitive functioning. These findings will help in identifying patients who are at risk for developing impaired health-related quality of life.

Aims: Many patients with repaired Tetralogy of Fallot (ToF) have right ventricular (RV) volume overload due to pulmonary regurgitation (PR). We studied the effect of volume overload on global and regional RV and left ventricular (LV) deformation, and their relationships with conventional diagnostic parameters., Methods and Results: In this cross-sectional study, 94 prospectively recruited ToF patients (61% male, age 32.8 ± 9.5 years, age at repair 1.9 [0.8-5.7] years, 39% pulmonary homograft) and 85 healthy controls of similar age and sex underwent echocardiography and electrocardiography. In a subset of patients, cardiac magnetic resonance imaging, bicycle ergometry, and NT-proBNP measurement were performed within the same day. With speckle-tracking echocardiography, we analysed peak systolic global longitudinal strain (GLS), segmental longitudinal strain and strain rate of the RV free wall, LV lateral wall, and septum. Patients had a lower RV free wall strain than controls (-18.1 ± 4.5 vs. -26.5 ± 4.5%, P < 0.001), especially at the apical segment (-15.9 ± 7.4 vs. -28.2 ± 7.7%, P < 0.001), and lower RV strain rate. LV GLS was also lower (-17.4 ± 2.5 vs. -19.6 ± 1.9%, P < 0.001), mainly due to the interventricular septum. Patients with PR >25% had higher LV GLS and RV free wall strain than patients with PR ≤25% (P = 0.004, P = 0.039, respectively). No relationships were found with NT-proBNP or exercise capacity., Conclusion: RV free wall strain and strain rate are decreased in adults late after ToF repair, especially at the apical segment suggesting that apical function is most affected in these RVs. Regarding the LV, septal strain is decreased indicating that RV dysfunction adversely affects LV function, probably by mechanical coupling of the ventricles., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: It is unknown whether right-ventricular (RV) volume overload caused by an atrial septal defect (ASD) still has its effect on RV deformation long after repair. We evaluated RV and left-ventricular (LV) deformation beyond 30 years after surgical ASD repair in childhood, and studied relationships with conventional diagnostic parameters., Methods and Results: In this prospective study, we included 102 subjects: 51 patients with repaired ASD (39% male, age 43.3 ± 4.9 years, age at repair 7.9 ± 3.6 years) and 51 healthy controls of similar age and sex. All subjects underwent echocardiography and electrocardiography. Additionally, ASD patients underwent cardiac magnetic resonance imaging (CMR), bicycle ergometry, and NT-proBNP measurement. With speckle-tracking echocardiography, we analysed peak systolic longitudinal strain of the RV lateral wall, LV lateral wall, and septum. RV lateral wall global longitudinal strain (GLS) was lower in patients (-20.4 ± 2.7%) than controls (-26.8 ± 4.2%, P < 0.001), due mainly to decreased apical strain (-19.3 ± 6.2 vs. -28.8 ± 8.3%, P < 0.001). RV lateral wall GLS correlated with CMR-derived RV and LV end-diastolic volumes (ρ = 0.49, P = 0.014; ρ = 0.53, P = 0.005), and with RV and LV end-systolic volumes (ρ = 0.43, P = 0.034; ρ = 0.46, P = 0.019). LV GLS was similar between patients and controls (P = 0.144). No significant correlations were found with NT-proBNP or exercise capacity., Conclusion: Although ASD repair was already performed in childhood, RV longitudinal strain, especially of the apical segment, is decreased in patients 35 years after surgery. This suggests that RV function has still been affected in the long run, probably due to the early RV volume overload, but possibly also as sequel of surgery., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

MRI is an important additional tool in the diagnostic work-up of children with congenital heart disease. This review aims to summarise the role MRI has in this patient population. Echocardiography remains the main diagnostic tool in congenital heart disease. In specific situations, MRI is used for anatomical imaging of congenital heart disease. This includes detailed assessment of intracardiac anatomy with 2-D and 3-D sequences. MRI is particularly useful for assessment of retrosternal structures in the heart and for imaging large vessel anatomy. Functional assessment includes assessment of ventricular function using 2-D cine techniques. Of particular interest in congenital heart disease is assessment of right and single ventricular function. Two-dimensional and newer 3-D techniques to quantify flow in these patients are or will soon become an integral part of quantification of shunt size, valve function and complex flow patterns in large vessels. More advanced uses of MRI include imaging of cardiovascular function during stress and tissue characterisation of the myocardium. Techniques used for this purpose need further validation before they can become part of the daily routine of MRI assessment of congenital heart disease.

Objective: To evaluate differences in functional parameters and reproducibility between short axis and axial slice orientation in the quantitative evaluation of the systemic right ventricle by cardiovascular magnetic resonance., Design: Cross-sectional evaluation comparing two methods (Bland-Altman)., Setting: Tertiary care outpatients., Interventions: Quantitative cardiovascular magnetic resonance evaluation using short axis or axial slice orientation., Main Outcome Measures: Intraobserver variance, interobserver variance and systematic differences in systemic right ventricular volumes, ejection fraction, and mass between both methods., Patients: Twenty-two patients (mean age 33 ± 7 years) with systemic right ventricle (three with congenitally corrected transposition of the great arteries and 19 with atrially switched transposition of the great arteries)., Results: Compared with short axis slices, analysis of axial slices resulted in higher end systolic volume (6.6%, P < .01), while mass (-10.8%, P < .01) and ejection fraction (-8.9%, P < .01) turned out lower. Intraobserver and interobserver reproducibility were similar for both methods when measuring end-diastolic and end-systolic volumes. However, ejection fraction and stroke volume were measured more consistently in axial orientation, while ventricular mass was measured more consistently in short axis orientation., Conclusion: There are significant differences in volume, mass, and function between measurements in axial and short axis orientation. Ejection fraction and stroke volume, which have a high clinical relevance, were measured more consistently in axial slice orientation. Consequently, we recommend using axial slice orientation in patients with a systemic right ventricle., (© 2014 Wiley Periodicals, Inc.)

Background: The perimembranous ventricular septal (pVSD) defect is the most common congenital heart disease phenotype. Several parental factors are associated with pVSD risk in the offspring. To contribute to the future prevention of pVSDs, we investigated associations with nongenetic parental conditions., Methods: In a case-control study with standardized data collection at 17 months after birth, 115 parents of a child with pVSD and 484 parents of a healthy child completed questionnaires about periconceptional nongenetic conditions. Univariable and multivariable logistic regression analyses were used to estimate odds ratios (OR) with 95% confidence intervals (95% CI)., Results: Complete data were available for 588 families (98%). Maternal risk conditions associated with pVSD offspring were a positive family history of congenital heart disease (OR, 2.61; 95%CI, 0.98-6.91), medication use (OR, 1.80; 95%CI, 1.13-2.85) and advanced age (OR, 1.07; 95%CI, 1.02-1.12). Exposure to phthalates (OR, 1.93; 95%CI, 1.05-3.54) was the only paternal risk condition associated with pVSD offspring., Conclusion: Four periconceptional parental conditions contributed to pVSD risk in the offspring. Couples planning pregnancy should be counseled on these risk conditions which are partially modifiable to contribute to the future prevention of pVSDs., (© 2014 Wiley Periodicals, Inc.)

Objectives: In patients with univentricular heart disease, the total cavopulmonary connection (TCPC) is the preferred treatment. TCPC can be performed using the intra-atrial lateral tunnel (ILT) or extracardiac conduit (ECC) technique. The purpose of the present study was to evaluate exercise capacity in contemporary TCPC patients and compare the results between the 2 techniques., Methods: A total of 101 TCPC patients (ILT, n=42; ECC, n=59; age, 12.2±2.6 years; age at TCPC completion, 3.2±1.1 years) underwent cardiopulmonary exercise testing. The patients were recruited prospectively from 5 tertiary referral centers., Results: For the entire group, the mean peak oxygen uptake was 74%±14%, peak heart rate was 90%±8%, peak workload was 62%±13%, and slope of ventilation versus carbon dioxide elimination (VE/VCO2 slope) was 127%±30% of the predicted value. For the ILT and ECC groups, patient age, age at TCPC completion, body surface area, peak workload, and peak heart rate were comparable. The percentage of predicted peak oxygen uptake was lower in the ILT group (70%±12% vs 77%±15%; P=.040), and the percentage of predicted VE/VCO2 slope was greater in the ILT group (123%±36% vs 108%±14%; P=.015). In a subgroup analysis that excluded ILT patients with baffle leak, these differences were not statistically significant., Conclusions: Common exercise parameters were impaired in contemporary Fontan patients. Chronotropic incompetence was uncommon. The peak oxygen uptake and VE/VCO2 slope were less favorable in ILT patients, likely related to baffle leaks in some ILT patients. These results have shown that a reduced exercise capacity in Fontan patients remains an important issue in contemporary cohorts. The ECC had a more favorable exercise outcome at medium-term follow-up., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate effects of an exercise program on health-related quality of life (HRQoL) in children and adolescents with tetralogy of Fallot (ToF) or a Fontan circulation., Methods: Stratified, randomized, controlled intervention study conducted in five participating centers of pediatric cardiology in The Netherlands. In total, 93 patients, aged 10-25 years, with surgical repair for tetralogy of Fallot or with a Fontan circulation for single-ventricle physiology were included. They were randomly allocated with a ratio of 2:1 to: (1) a 12-week period with an exercise program for 3 times per week or (2) to a control group. Randomization was stratified by age, gender, and cardiac diagnosis. At baseline and follow-up after 12 weeks, all participants completed Web-based age-appropriate HRQoL questionnaires. Primary analyses involved change in HRQoL during follow-up. Secondary analyses concerned influence of cardiac diagnosis and comparison with normative data., Results: Forty-eight (86%) and 32 (86%) patients in the exercise-group and control-group respectively completed all questionnaires at baseline and follow-up. Compared with the control-group, children, aged 10-15 years, in the exercise-group improved significantly on self-reported cognitive functioning, p < .05, r = .30, and parent-reported social functioning, p < .05, r = .30. Youngsters aged 16-25 years did not change their HRQoL. Cardiac diagnosis had no influence on pre/post changes. Children and youngsters in this study reported comparable or better HRQoL than norm groups., Conclusions: Participation in an exercise program improved HRQoL of children with ToF or a Fontan circulation, especially in those with low baseline QoL., (Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Low birth weight is associated with cardiovascular disease in adulthood. Hemodynamic adaptations related to fetal growth restriction may underlie these associations, through persistent influences on cardiovascular development. We examined the associations of third trimester fetal hemodynamics with cardiovascular outcomes in childhood., Methods: In a prospective cohort study among 917 pregnant women and their children, we measured fetal growth, and fetal arterial and cardiac hemodynamic variables with ultrasound and Doppler examinations at a gestational age of 30.3 (95% range 28.8-32.3) weeks. At the age of 6 years, we measured blood pressure, carotid-femoral pulse wave velocity, and left cardiac structures and function., Results: We observed that fetal hemodynamics were not associated with childhood blood pressure and carotid-femoral pulse wave velocity. The fetal aorta ascendens diameter and left cardiac output were positively associated with childhood aortic root diameter [0.14 standard deviation score (SDS), 95% confidence interval (CI) 0.07-0.22 and 0.08 SDS, 95% CI 0.01-0.15 per SDS change in diameter and output, respectively]. Fetal left ventricular diastolic filling pattern was inversely associated with aortic root diameter (-0.07 SDS, 95% CI -0.13 to 0.00 per SDS change in E/A ratio) at 6 years. Analyses adjusted and stratified for estimated fetal weight showed no differences in results., Conclusion: Our results suggest that third trimester fetal vascular resistance parameters do not affect blood pressure or arterial stiffness in childhood. Fetal cardiac functional and structural measures are associated with cardiac outcomes in childhood. Whether these early adaptations lead to greater risks of cardiovascular disease should be further studied.

Aims: Left ventricular (LV) dysfunction is a major determinant of late adverse clinical outcome in adult patients with tetralogy of Fallot (ToF). Therefore, early detection is important. Speckle-tracking echocardiography (STE) has emerged as a quantitative technique to assess LV function. The aim of this study was to evaluate LV rotation and twist with STE in adult ToF patients and their association with right ventricular (RV) and LV dimensions and function, exercise capacity, and NT-proBNP level., Methods: Eighty-two ToF patients and 56 healthy controls matched for age and gender underwent echocardiography, electrocardiography, cardiac magnetic resonance imaging (CMR), bicycle ergometry, and NT-proBNP measurement. For STE, short-axis parasternal views were obtained at the LV base and apex. We analysed LV apical and basal rotation curves and calculated LV twist., Results: Of the 82 ToF patients (55% male, age 33 ± 10 years, 98% NYHA I), 58 (71%) had normal twist, but lower than the controls [12.5 (IQR: 6.6) vs. 16.9 (IQR: 8.2) degrees, P = 0.002] mainly due to decreased apical rotation. Twenty-one (26%) patients had abnormal apical rotation which was associated with larger LV dimensions and decreased systolic biventricular function. Multivariable regression analyses showed positive relations of LV twist with biventricular systolic function measured with echocardiography as well as CMR., Conclusion: The majority of adults with corrected ToF show a reduced LV twist. Strikingly, one-quarter of these patients have an abnormal apical rotation which is associated with decreased systolic LV and RV function. These findings suggest that abnormal apical rotation is a new objective diagnostic criterion for detection of ventricular dysfunction.

Aims: To evaluate the additional value of dobutamine stress testing in patients with repaired tetralogy of Fallot (TOF) by relating stress imaging parameters at baseline to relevant parameters of clinical condition and right ventricular (RV) size during a serial follow-up., Methods and Results: We prospectively included 27 patients (14 ± 4 years at baseline), who were studied twice with a 5-year interval. Patients underwent cardiovascular magnetic resonance imaging to assess RV systolic and diastolic function at rest and during dobutamine stress. Normal response to dobutamine was defined as a decrease in RV end-systolic volume, and a increase in RV ejection fraction (EF) during stress. Exercise testing and electrocardiography were performed to determine peak oxygen uptake (peak VO₂), QRS duration, and QT interval corrected for heart rate (QTc) interval. RV volumes, QRS duration, and QTc interval increased significantly from baseline to follow-up; peak VO₂ tended to decrease (95 ± 20-89 ± 14%, P = 0.086). Response to dobutamine was normal in 26 of 27 patients and remained stable during the follow-up [relative increase in RVEF during stress: +25 ± 9% (baseline) vs. +27 ± 10% (follow-up)]. A smaller relative increase in RVEF during stress at baseline related to a larger relative decrease in peak VO₂ during the follow-up (r = 0.59, P = 0.004). No significant associations were found with the relative increase in QRS duration, QTc interval, or RV end-diastolic volume during a 5-year follow-up., Conclusion: In a young TOF population, response to dobutamine stress was normal and remained stable during the 5-year follow-up. A smaller increase in RVEF during stress at baseline was predictive for a larger decrease in peak VO₂ during the 5-year follow-up.

Objective: To study the changes over time in biventricular size and function, and clinical parameters in patients after repair of tetralogy of Fallot (TOF) without subsequent pulmonary valve replacement (PVR)., Methods: We prospectively included 78 non-PVR patients (age 20(6-60)years at baseline), who were studied twice with a 5-year interval. Patients underwent magnetic resonance imaging for assessment of biventricular size and function. Exercise testing and electrocardiography were performed to determine peak oxygen uptake (peak VO2) and QRS duration. N-terminal prohormone brain natriuretic peptide (NT-proBNP) was assessed additionally., Results: Pulmonary regurgitation (PR), right ventricular (RV) volumes and QRS duration increased during 5-year follow-up (RV end-diastolic volume (EDV) 130 ± 30 ml/m(2) to 138 ± 34 ml/m(2); QRS 132 ± 27 msec to 139 ± 27 msec); peak VO2 decreased (96 ± 19% to 91 ± 17%). RV ejection fraction, RV effective stroke volume (eff.SV), and NT-proBNP levels remained unchanged. The slope of RVEDV increase was 1.6 ± 3.0 ml/m(2)/year, and depended on RVeff.SV, not on RVEDV, at baseline. Increase in RVEDV correlated with increase in QRS duration over time (r=0.28, p=0.016), and with decrease in RV mass/EDV ratio over time (r=-0.42, p<0.001), not with decrease in peak VO2. In subgroup analysis, patients with larger RVs at baseline showed larger increase in PR during follow-up and larger decrease in NYHA class over time., Conclusions: In TOF patients with moderate RV dilatation, RVEDV increased by 1.6 ± 3.0 ml/m(2)/year, irrespective of RV size at baseline, but depended on RVeff.SV at baseline. Despite limited progression in RV size, unfavourable changes occurred during 5 years follow-up, which suggests there is a need for close follow-up., (© 2013.)

AIM.: The study aims to describe the long-term cardiological and psychological results of our first surgical cohort of arterial switch operation (ASO) patients and compare the results with our earlier series of Mustard patients. METHODS.: Twenty-four survivors of ASO operated in our center (1985-1990) were evaluated by electrocardiography, echocardiography, magnetic resonance imaging, exercise testing, 24-hour Holter-monitoring, and health-related quality of life questionnaire. The results were compared with 58 adult Mustard patients who were evaluated in 2001 using the same study protocol. RESULTS.: Arterial switch operation was performed at a median age of 13 days and Mustard operation at 2 years. Median follow-up was 22 years (range 20-25) and 25 years (22-29), respectively. After ASO, survival was better (P =.04). The event-free survival after 22 years was 77% after ASO vs. 44% after Mustard (P =.03). Good systemic ventricular function was present in 93% after ASO vs. 6% after Mustard (P <.01). Exercise capacity in ASO was 85% of predicted, compared with 72% in Mustard patients (P =.01). Aortic regurgitation was found in 21% of ASO patients vs. 16% in Mustard patients. Arterial switch patients vs. Mustard patients reported significantly better quality of life and less somatic complaints. CONCLUSION.: The progression made in surgical treatment for transposition of the great arteries from Mustard to ASO has had a positive impact on survival, cardiac function, exercise capacity, and also self-reported quality of life and somatic complaints. Longer follow-up is warranted to monitor aortic regurgitation., (© 2013 Wiley Periodicals, Inc.)

Background: A reference set of data of normal values of newly developed cardiopulmonary parameters of exercise testing in an 8-18-year-old population is lacking., Patients and Methods: Cardiopulmonary exercise testing was performed in 175 healthy school children (8-18 years old). Continuous electrocardiography was performed, and minute ventilation, oxygen uptake (VO2), and carbon dioxide (CO2) production were measured continuously with a respiratory gas analysis system., Results: Peak VO2/kg did not change with age, whereas the ventilation to carbon dioxide exhalation slope was lower in the older children. The decline in heart rate during recovery was much faster in the youngest children. Linear regression analysis showed a significant effect of age on: peak work rate (WRpeak) and WRpeak/kg, ventilation to carbon dioxide exhalation slope, heart rate recovery, and VO2peak (boys only) (All P < 0.001). The ΔVO2/ΔWR slope remained constant throughout all age groups., Conclusion: This study comprehensively provides a reference set of data for the most important cardiopulmonary variables that can be obtained during exercise testing in children.

Unlabelled: Endocardial cushion defects (ECDs) of the cardiac outflow tract are among the most common congenital heart disease phenotypes. VEGF is essential for endocardial cushion formation and derangements in VEGF synthesis lead to ECD. Three functional single nucleotide polymorphisms (SNPs) in the VEGF gene -2578 C>A, -1154 G>A, and -634 G>C play a role in cardiogenesis. In a Dutch case-control family study of triads, 190 case and 317 control children with both parents, we investigated linkage and association between these VEGF SNPs and ECD. Allele frequencies for the three VEGF SNPs were comparable between ECD children and controls. However, VEGF alleles -2578 C and -1154 G were transmitted more frequently to children with ECD (p = 0.003 and p = 0.002), in particular perimembranous ventricular septal defects (p = 0.012 and p = 0.006). The -2578A/-1154A/-634G haplotype was associated with a reduced risk of ECD (OR 0.7; 95% CI, 0.6-1.0) and was significantly less transmitted to children with ECD (p = 0.002). In a Dutch population, we show that the VEGF 2578 C, -1154 G alleles, and the AAG haplotype are associated with ECD. Possible VEGF gene-environment interactions exposures are discussed., Abbreviations: :

Purpose: To assess normal values for biventricular function, volumes, and mass with current cardiovascular magnetic resonance (CMR) imaging sequences in children., Materials and Methods: Included in the study were 60 healthy children aged 8-17 years. A short axis set of contiguous slices was acquired with CMR imaging employing steady-state free precession. Biventricular end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), and mass were determined. Uni- and multivariate linear regression analyses were performed to study the interrelation of age, gender, and body surface area (BSA) on biventricular volumes and mass. The coefficient of variation was calculated for intra- and interobserver variability., Results: EF did not differ between boys and girls (mean LV-EF 69+/-(SD) 5%, mean RV-EF 65+/-5%). BSA had good (EDV, mass) and modest (ESV) correlation with biventricular measurements. Gender appeared a significant modifier of these relations, whereas age had no independent contribution. The intra- and interobserver coefficient of variation was in the range 2.1%-13.9% for biventricular EDV, ESV, and mass., Conclusion: This study reveals gender-specific normative data for biventricular function, volumes, and mass in children age 8-17 years that can be used as reference data in the follow-up of pediatric cardiac patients., (Copyright (c) 2009 Wiley-Liss, Inc.)

Purpose: To assess pulmonary artery (PA) size, flow variables, and wall shear stress (WSS) in patients after Fontan operation at a young age., Materials and Methods: Flow in the branch PA was obtained with phase contrast velocity-encoded cardiovascular magnetic resonance imaging in 14 patients before and after low-dose dobutamine stress (7.5 microg/kg/min) and in 17 healthy controls at rest., Results: At rest, stroke index, total flow, average, and peak flow rate were all statistically significantly lower in patients than in controls (P<0.001). With stress-testing, all variables increased in patients (P<0.001), apart from stroke index, which did not change. At rest, branch PA area did not differ between patients and controls. Distensibility was lower in patients than in controls (P<0.001). With stress-testing, area and distensibility did not change. At rest, WSS was lower in patients than in controls (P<0.001). WSS increased with stress-testing (P<0.001), but not to the same levels as during resting conditions of the control group., Conclusion: PA size is normal long-term after Fontan operation at a young age. Flow variables, distensibility, and WSS are significantly lower compared to healthy controls, and do not show adequate reactions with stress-testing, which is suggestive of pulmonary artery endothelial and/or vascular dysfunction., (Copyright (c) 2008 Wiley-Liss, Inc.)

Context: In Turner syndrome (TS), GH treatment is well established. Data on cardiac status after discontinuation of treatment are scarce. This study aimed to assess biventricular size and function in TS at least 6 months after discontinuation of GH treatment., Methods: TS patients and healthy women prospectively underwent cardiac magnetic resonance imaging. Ventricular two-dimensional tomographic cine data were acquired to obtain biventricular volume, mass, and ejection fraction. Atrioventricular valve flow measurements were performed using a two-dimensional flow-sensitized sequence. Flow velocity curves were calculated and indices of biventricular diastolic filling were derived., Results: Thirty-one patients [mean (sd) age 20 (2) yr, body surface area 1.75 (0.15) m(2), 5 (2) yr after GH discontinuation] and 23 normal control women [age 21 (2) yr, body surface area 1.80 (0.13) m(2)] were included. Compared with controls, patients had smaller mean end-diastolic volumes [right ventricle (RV), 84 (11) ml/m(2) vs. 79 (10), P = 0.02; left ventricle (LV), 81 (10) vs. 72 (9), P < 0.001], end-systolic volumes [RV 38 (7) ml/m(2) vs. 36 (6), P = 0.04; LV 34 (5) vs. 29 (4), P < 0.001], and stroke volumes [RV 46 (6) ml/m(2) vs. 43 (6), P = 0.03; LV, 47 (7) vs. 44 (4), P = 0.02]. Patients had a higher mean heart rate [79 (13) beats/min vs. 71 (10), P < 0.05]. Biventricular ejection fraction, mass, cardiac output, and diastolic filling pattern were comparable., Conclusion: After discontinuation of GH treatment TS patients showed no myocardial hypertrophy and well-preserved biventricular function. Ventricular volumes were smaller in Turner patients, compared with controls, whereas mean heart rate was higher. These last observations may be part of the natural development in TS and not linked to GH treatment, which at this point we consider safe.

Aims: Congenital heart defects (CHDs) have a multifactorial origin, in which subtle genetic factors and peri-conception exposures interact. We hypothesize that derangements in the homocysteine and detoxification pathways, due to a polymorphism in the nicotinamide N-methyltransferase (NNMT) gene, low maternal dietary nicotinamide intake, and medicine use in the peri-conception period, affect CHD risk., Methods and Results: In 292 case and 316 control families, maternal peri-conception medicine use and low dietary intake of nicotinamide (

Myocardial hyperplasia is generally considered to occur only during fetal development. However, recent evidence suggests that this type of response may also be triggered by cardiac overload after birth. In congenital heart disease, loading conditions are frequently abnormal, thereby affecting ventricular function. We hypothesized that chronic right ventricular pressure overload imposed on neonatal hearts initiates a hyperplastic response in the right ventricular myocardium. To test this, young lambs (aged 2-3 weeks) underwent adjustable pulmonary artery banding to obtain peak right ventricular pressures equal to left ventricular pressures for 8 weeks. Transmural cardiac tissue samples from the right and left ventricles of five banded and five age-matched control animals were studied. We found that chronic right ventricular pressure overload resulted in a twofold increase in right-to-left ventricle wall thickness ratio. Morphometric right ventricular myocardial tissue analysis revealed no changes in tissue composition between the two groups; nor were right ventricular myocyte dimensions, relative number of binucleated myocytes, or myocardial DNA concentration significantly different from control values. In chronic pressure overloaded right ventricular myocardium, significantly (P < 0.01) more myocyte nuclei were positive for the proliferation marker proliferating cellular nuclear antigen than in control right ventricular myocardium. Chronic right ventricular pressure overload applied in neonatal sheep hearts results in a significant increase in right ventricular free wall thickness which is primarily the result of a hyperplastic myocardial response.

Objective: Right ventricular pressure overload occurs in several types of (congenital) heart disease, as well as in pulmonary disease. Clinical outcome in some of these patient groups might in part be related to left ventricular loading conditions. The effects of left ventricular unloading on the function of the hypertrophic right ventricle have not been studied. We aimed to study the effects of left ventricular unloading on right ventricular hemodynamics and contractility in an animal model of chronic right ventricular pressure overload., Methods: In lambs the pulmonary artery was chronically banded to increase right ventricular pressure to systemic levels. After 8 weeks, right ventricular contractility and hemodynamic function were assessed in these lambs, as well as in age-matched control animals, by using a combined pressure-conductance catheter in the right ventricle during baseline conditions and during complete bypass of the left ventricle., Results: In both groups acute left ventricular unloading significantly decreased left ventricular pressure to low levels while aortic pressure was maintained. In the right ventricle of the control group, both end-systolic and end-diastolic volumes increased with left ventricular unloading (P <.01) while end-systolic pressure was maintained. Cardiac output was unchanged despite decreased right ventricular contractility. In the banding group acute left ventricular unloading also decreased right ventricular contractility but increased cardiac output. During acute left ventricular unloading, diastolic stiffness was unchanged in the control group, whereas it was significantly decreased in the banding group., Conclusions: Both in normal hearts and in hearts subject to chronic right ventricular pressure overload, acute left ventricular unloading decreases right ventricular contractility. Although no effects on cardiac output are encountered in normal hearts during left ventricular bypass, cardiac output is improved in right ventricular pressure-overloaded hearts, most likely related to improved right ventricular diastolic compliance.

Objective: Banding of the pulmonary artery might be required to prevent pulmonary vascular damage in patients with increased pulmonary artery flow and to retrain the left ventricle in preparation for an arterial switch operation in patients with congenitally corrected transposition of the great arteries. Readjustment of the pulmonary artery band might be required in the postoperative period. In this study we aimed to test the feasibility of a novel device for bidirectionally adjustable pulmonary artery constriction., Methods: A hydraulic main pulmonary artery occluder was implanted in lambs and gradually inflated to create right ventricular pressure overload at a systemic (aortic) level. During the following period (up to 12 weeks), this pressure overload was monitored by measuring aortic and right ventricular pressures by means of implanted subcutaneous reservoirs. If required to maintain the right ventricular pressure overload at a systemic level in the growing animals, the occluder was deflated through a third subcutaneous reservoir., Results: After the banding period (average of 64 +/- 8 days), the main pulmonary artery cuff could still be adjusted, and the animals showed no clinical signs of heart failure. Histologic analysis of the pulmonary artery showed extensive fibrosis, a giant cell response around the device, and small areas of tissue necrosis; complete transmural necrosis was not detected., Conclusions: This device allows adjustment of the pulmonary artery cuff in a precise manner over a prolonged period of time without surgical reintervention. Potentially, the device might have applications for clinical use in children with congenital heart disease.