A 12-week lifestyle intervention: effects on fatigue, fear, and nutritional status in children with a Fontan circulation.

Introduction: Children and adolescents with a Fontan circulation are less physically active compared to healthy peers. In the current study, effects of a 12-week lifestyle intervention on fatigue, fears regarding exercise, caloric intake, rest energy expenditure (REE), and body composition were measured in children with a Fontan circulation. Methods: This study was a semi-cross-over randomized controlled trial. The lifestyle intervention consisted of a 12-week high-weight resistance training (three supervised training sessions a week) supported by high-protein diet (>2 g/kg) and tailored recommended caloric intake. Fatigue (measured by the validated PedsQol Multidimensional Fatigue Scale), fears regarding exercise (measured on a fear thermometer), REE (measured using indirect calorimetry), caloric intake and body composition using air displacement plethysmography, and four-skinfold method were measured before and after the intervention and control period. Results: Twenty-seven pediatric Fontan patients, median age 12.9 years (IQR: 10.5-16.2), of the included 28 patients successfully completed the program. Before training, both child- and parent-reported levels of fatigue were significantly worse on all domains (general, sleep/rest, and cognitive fatigue) compared to healthy peers. After training, parent-reported fatigue significantly improved on the general and cognitive fatigue domains [effect size +16 points (7-25), p < 0.001, and +10 points (2-17), p = 0.015, compared to the control period]. Before training, fear regarding exercise scored on the fear thermometer was low for both children and parents (median score 1 and 2, respectively, on a scale of 0-8). After training, child-reported fear decreased further compared to the control period [effect size -1.4 points (-2.3 to -0.6), p = 0.001]. At baseline, children had increased REE +12% compared to reference values, which did not change after exercise. Children ate an average of 637 calories below recommended intake based on REE, caloric deficit became smaller after the intervention, and protein intake increased compared to the control period [-388 calories (-674 to -102), p = 0.008, and +15 g (0.4-30), p = 0.044]. Body fat percentage did not change significantly. Conclusion: A 12-week lifestyle intervention improved parent-reported fatigue symptoms in the children, further decreased child-reported fears, and increased caloric and protein intake.

Cardiac Function and Serum Biomarkers throughout Staged Fontan Palliation: A Prospective Observational Study.

Fontan patients undergo multiple cardiothoracic surgeries in childhood. Following these procedures, ventricular function is temporarily decreased, and recovers over months. This is presumably related to cardiopulmonary bypass, but this is incompletely understood. Throughout the Fontan palliation, cardiac function is also affected by volume unloading. We aimed to gain insight into the biological processes related to impaired ventricular function and recovery following Fontan palliations using a panel of biomarkers. Furthermore, we described changes in ventricular function across the Fontan palliation due to volume unloading. We performed a prospective multicenter observational study in patients undergoing partial (PCPC) or total cavo-pulmonary connection (TCPC). Patients underwent assessment-including echocardiography and blood sampling-before surgery (T1), at first follow-up (T2), and 1 year after their procedures (T3). Blood samples were analyzed using a biomarker panel (OLINK CVD-III). Ninety-two biomarkers were expressed as principal components (PC) to limit multiple statistical testing. We included 32 PCPC patients aged 7.2 [5.3-10.3] months, and 28 TCPC patients aged 2.7 [2.2-3.8] years. The single ventricular longitudinal strain (SV GLS) temporarily decreased for PCPC patients at T2 (-15.1 ± 5.6 (T1) to -13.5 ± 5.2 (T2) to -17.3 ± 4.5 (T3), p < 0.047 for all differences), but not following TCPC. The serum biomarkers were expressed as 4 PCs. PC1, including biomarkers of cell-cell adhesion, was not related to any patient characteristic. PC2, including biomarkers of superoxide anion regulation, increased at T2. PC3, including biomarkers of cardiovascular development, related to the stage of Fontan palliation. PC4 was of uncertain biological or clinical significance. No PC was found that related to ventricular performance. The SV GLS was temporarily diminished following PCPC, but not following TCPC. Several biomarkers were related to post-operative stress and adaptation to the PCPC or TCPC circulation, but none were related to the outcome.

Executive functioning of patients with congenital heart disease: 45 years after surgery.

BACKGROUND: Nowadays, more than 90% of patients with congenital heart disease (CHD) reach adulthood. However, long-term impact on neurodevelopment and executive functioning in adults with CHD are not completely understood. PURPOSE: To investigate the self- and informant-reported executive functioning in adults with CHD operated in childhood. MATERIAL AND METHODS: Longitudinal study of a cohort of patients (n = 194, median age: 49.9 [46.1-53.8]) who were operated in childhood (< 15 years old) between 1968 and 1980 (median follow-up time: 45 [40-53] years) for one of the following diagnoses: atrial septal defect (ASD), ventricular septal defect (VSD), pulmonary stenosis (PS), tetralogy of Fallot (ToF) or transposition of the great arteries (TGA). Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) questionnaire was used to assess self- and informant-reported executive functioning. RESULTS: 40-53 years after surgery, the CHD group did show significantly better executive functioning compared to the norm data. No significant difference was found between mild CHD (ASD, VSD and PS) and moderate/severe CHD (ToF and TGA). Higher education, NYHA class 1 and better exercise capacity were associated with better self-reported executive functioning, whereas females or patients taking psychiatric or cardiac medications reported worse executive functioning. CONCLUSIONS: Our findings suggest favorable outcomes (comparable to normative data) regarding executive functioning in adults with CHD, both self- and informant-reported. However, further study is warranted to explore more in detail the different cognitive domains of executive functioning in these patients.

Effects of enzyme replacement therapy on cardiac function in classic infantile Pompe disease.

OBJECTIVE: Patients with classic infantile Pompe disease are born with a hypertrophic cardiomyopathy, which resolves after treatment with Enzyme replacement therapy (ERT). We aimed to assess potential deterioration of cardiac function over time using myocardial deformation analysis. METHODS: Twenty-seven patients treated with ERT were included. Cardiac function was assessed at regular time intervals (before and after start with ERT) using conventional echocardiography and myocardial deformation analysis. Separate linear mixed effect models were used to asses temporal changes within the first year and the long-term follow-up period. Echocardiograms of 103 healthy children served as controls. RESULTS: A total of 192 echocardiograms were analyzed. Median follow-up was 9.9 years (IQR: 7.5-16.3). Mean LVMI before start of ERT was increased 292.3 g/m2 (95% CI: 202.8-381.8, mean Z-score + 7.6) and normalized after 1 year of ERT 87.3 g/m2 (CI: 67.5-107.1, mean Z-score + 0.8, p < 0.001). Mean shortening fraction was within normal limits before start of ERT, up to 22 years of follow-up. Cardiac function measured by RV/LV longitudinal, and circumferential strain was diminished before start of ERT, but normalized (<-16%) within 1 year after start of ERT, and all remained within normal limits during follow-up. Only LV circumferential strain gradually worsened in Pompe patients (+0.24%/year) during follow-up compared to controls. LV longitudinal strain was diminished in Pompe patients, but did not change significantly over time compared to controls. CONCLUSION: Cardiac function, measured using myocardial deformation analysis, normalizes after start of ERT, and seems to remain stable over a median follow-up period of 9.9 years.

Daily life and psychosocial functioning of adults with congenital heart disease: a 40-53 years after surgery follow-up study.

INTRODUCTION: Nowadays, more than 90% of patients with congenital heart disease (CHD) reach adulthood. However, knowledge about their psychosocial functioning is limited. METHODS: Longitudinal cohort study of patients (n = 204, mean age: 50 years, 46.1% female) who were operated during childhood (< 15 years) between 1968 and 1980 for one of the following diagnoses: atrial septal defect, ventricular septal defect, pulmonary stenosis, tetralogy of Fallot or transposition of the great arteries. Psychosocial functioning was measured every 10 years, using standardized and validated questionnaires. Results were compared with the general Dutch population and over time. RESULTS: After a median follow-up of 45 [40-53] years adults with CHD had a significantly lower educational level, occupation level and employment rate, but better health-related quality of life and emotional functioning compared with normative data. Patients with moderate/severe defects reported significantly more self-perceived physical restrictions and lack of physical strength due to their CHD. Compared to 2011, in 2021 patients considered their CHD as more severe and they felt more often disadvantaged. CONCLUSIONS: Overall, despite a lower education, occupation level and employment rate, our sample of patients with CHD had a positive perception of their life and  their psychosocial functioning was even better than the norm. Although the quality of life was very good, their view on their disease was more pessimistic than 10 years ago, especially for patients with moderate/severe CHD.

Fate of the Arterial Origin of Major Aortopulmonary Collateral Arteries After Unifocalization.

BACKGROUND: During unifocalization procedures for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries, collateral arteries are either ligated or detached. Not much is known of the fate of the remaining arterial origins in the long term. Available computed tomography (CT) or magnetic resonance (MR) imaging of the intrathoracic arteries was examined to investigate possible abnormalities at the former position of the collateral arteries as well as ascending aortic diameters. METHODS: From 1989 to 2018, we performed 66 unifocalization procedures in 39 patients. One hundred and twenty-nine collateral arteries were ligated or detached. In 52% (15) of the surviving patients (with a total of 55 ligated or detached collaterals), sufficient imaging of the thoracic aorta from CT (11) and/or MR (9) was available for evaluation. RESULTS: The median interval between unifocalization procedure and imaging was 15 years (interquartile range [IQR]: 9-19 years). In 93% (14) of the scanned patients, 18 blunt ends were detected at the location of a former collateral artery. No aneurysm formation of the descending aorta was observed. The median diameter of the ascending aorta was 35 mm (IQR: 31-40 mm). During follow-up, no aortic dissection or rupture occurred. CONCLUSIONS: Aortic imaging late after unifocalization showed abnormalities in 93% of the scanned patients. Abnormalities consisted mostly of blunt ends of the former collateral artery. We recommend to include routine imaging of the aorta during late follow-up to detect eventual future abnormalities and monitor aortic diameters. Ascending aortic diameters showed slight dilatation with no clinical implications so far.

Multicentre reference values for cardiac magnetic resonance imaging derived ventricular size and function for children aged 0-18 years.

AIMS: Cardiovascular magnetic resonance (CMR) imaging is an important tool in the assessment of paediatric cardiac disease. Reported reference values of ventricular volumes and masses in the paediatric population are based on small cohorts and several methodologic differences between studies exist. We sought to create steady-state free precession (SSFP) CMR reference values for biventricular volumes and mass by combining data of previously published studies and re-analysing these data in a standardized manner. METHODS AND RESULTS: A total of 141 healthy children (68 boys) from three European centres underwent cine-SSFP CMR imaging. Cardiac structures were manually contoured for end-diastolic and end-systolic phases in the short-axis orientation according to current standardized CMR post-processing guidelines. Volumes and masses were derived from these contours. Age-related reference curves were constructed using the lambda mu sigma method. Median age was 12.7 years (range 0.6-18.5). We report biventricular volumes and masses, unindexed and indexed for body surface area, stratified by age groups. In general, boys had approximately 15% higher biventricular volumes and masses compared with girls. Only in children aged <6 years old no gender differences could be observed. Left ventricle ejection fraction was slightly higher in boys in this study population (median 67% vs. 65%, P = 0.016). Age-related reference curves showed non-linear relations between age and cardiac parameters. CONCLUSION: We report volumetric SSFP CMR imaging reference values for children aged 0-18 years old in a relatively large multi-centre cohort. These references can be used in the follow-up of paediatric cardiac disease and for research purposes.

A compromised maternal vitamin D status is associated with congenital heart defects in offspring.

BACKGROUND: Interactions between genetic and environmental factors, including modifiable maternal nutrition and lifestyle, play a significant role in the pathogenesis of most congenital heart defects (CHD). The aim of this study was to investigate associations between periconceptional maternal vitamin D status and the prevalence of CHD in offspring. METHODS: A case-control study was performed in 345 mothers of a child with CHD and 432 mothers of a child without CHD from four tertiary hospitals in the Netherlands between 2003 and 2005. Approximately 15months after pregnancy mothers filled out questionnaires regarding general characteristics and periconceptional lifestyle. Maternal blood was obtained to determine serum 25-hydroxyvitamin D and lipid concentrations. The 25-hydroxyvitamin D concentration was stratified into a deficient <50nmol/l, moderate 50-75nmol/l and adequate >75nmol/l status. Logistic regression was performed to study associations between vitamin D status and CHD risk, adjusted for maternal age, body mass index, ethnicity, smoking and total cholesterol concentration. RESULTS: Case mothers less often had an adequate vitamin D status compared with controls (27% vs. 38%; p=0.002). The use of multivitamin supplements, ethnicity, season and body mass index were associated with vitamin D concentrations. A moderate (odds ratio 1.58, [95%CI 1.08, 2.32]) and deficient (odds ratio 2.15, [95%CI 1.44-3.19]) vitamin D status were associated with CHD in offspring. CONCLUSION: A compromised maternal vitamin D status is associated with an approximately two-fold increased prevalence of CHD in offspring. Therefore, improvement of the periconceptional maternal vitamin D status is recommended.

Longitudinal Myocardial Deformation Does Not Predict Single Ventricle Ejection Fraction Assessed by Cardiac Magnetic Resonance Imaging in Children with a Total Cavopulmonary Connection.

Survival of children with single ventricle heart defects after the total cavopulmonary connection (TCPC) has improved, but impaired cardiac function remains a major cause of morbidity and mortality. Cardiac magnetic resonance imaging (cMRI) is the gold standard in assessing single ventricle volume and function, but high costs and limited availability hamper its routine use. A cheaper and more available alternative is echocardiography. Myocardial function can be studied in more detail using speckle tracking echocardiography (STE). The purpose of the study was to describe the association between myocardial deformation assessed by speckle tracking echocardiography (STE) and single ventricle function assessed by cMRI and to evaluate differences in myocardial deformation in children with single left and single right ventricular morphology. Cross-sectional, multicenter study in 77 children after TCPC was conducted. STE segmental and global longitudinal peak strain and systolic strain rate (SR) of the dominant ventricle were measured. Impaired SV function by cMRI was defined as ejection fraction (EF) < 45%. Mean age was 11.8 (range 9.7-14.3) years. Pearson R for cMRI EF versus global longitudinal strain and SR was - 0.25 (p = 0.06) and - 0.03 (p = 0.82), respectively. Global single ventricle longitudinal strain and SR was similar in patients after TCPC with single left and single right ventricular morphology (- 19.0 ± 3.1% vs 19.2 ± 3.2%, p = 0.94). STE myocardial deformation parameters do not correlate with single ventricle ejection fraction assessed by cMRI.

KinCor, a national registry for paediatric patients with congenital and other types of heart disease in the Netherlands: aims, design and interim results.

OBJECTIVE: Studies in children with heart disease have been hampered by a lack of easily identifiable patient groups. Currently, there are few prospective population-based registries covering the entire spectrum of heart disease in children. KinCor is a Dutch national registry for children with heart diseases. This paper presents the aims, design and interim results of the KinCor project. METHODS: All children presenting at a Dutch university medical centre with a diagnosis of heart disease from 2012 onwards were eligible for registration in the KinCor database. Data entry is through a web-based portal. Entry codes have been synchronised with the European Paediatric Cardiac Coding system, allowing coupling with similar databases for adults, such as CONCOR. RESULTS: Between June 2012 and July 2015, 8421 patients were registered (76 % of those eligible). Median age of the patients was 9.8 years, 44.7 % were female; 6782 patients had morphological congenital heart disease. The most prevalent morphological congenital heart defects were ventricular septal defects (18 %), Tetralogy of Fallot (10 %) and transposition of great arteries (9 %). For 42 % of the patients additional diagnoses were registered. Sixty percent of patients had undergone at least one intervention (catheter intervention or surgery). CONCLUSION: The KinCor database has developed into a large registry of data of children with all types of heart disease and continues to grow. This database will provide the opportunity for epidemiological research projects on congenital and other types of heart disease in children. Entry codes are shared with the CONCOR database, which may provide a unique dataset.

Maternal obesity, gestational weight gain and childhood cardiac outcomes: role of childhood body mass index.

BACKGROUND: Maternal obesity may affect cardiovascular outcomes in the offspring. We examined the associations of maternal prepregnancy body mass index and gestational weight gain with childhood cardiac outcomes and explored whether these associations were explained by parental characteristics, infant characteristics or childhood body mass index. METHODS: In a population-based prospective cohort study among 4852 parents and their children, we obtained maternal weight before pregnancy and in early, mid- and late pregnancy. At age 6 years, we measured aortic root diameter (cm) and left ventricular dimensions. We calculated left ventricular mass (g), left ventricular mass index (g m(-2.7)), relative wall thickness ((2 × left ventricular posterior wall thickness)/left ventricular diameter), fractional shorting (%), eccentric left ventricular hypertrophy and concentric remodeling. RESULTS: A one standard deviation score (SDS) higher maternal prepregnancy body mass index was associated with higher left ventricular mass (0.10 SDS (95% confidence interval (CI) 0.08, 0.13)), left ventricular mass index (0.06 SDS (95% CI 0.03, 0.09)) and aortic root diameter (0.09 SDS (95% CI 0.06, 0.12)), but not with relative wall thickness or fractional shortening. A one SDS higher maternal prepregnancy body mass index was associated with an increased risk of eccentric left ventricular hypertrophy (odds ratio 1.21 (95% CI 1.03, 1.41)), but not of concentric remodeling. When analyzing the effects of maternal weight in different periods simultaneously, only maternal prepregnancy weight and early pregnancy weight were associated with left ventricular mass, left ventricular mass index and aortic root diameter (P-values<0.05), independent of weight in other pregnancy periods. All observed associations were independent of parental and infant characteristics, but attenuated to non-significance after adjustment for childhood body mass index. CONCLUSION: Maternal prepregnancy body mass index and weight gain in early pregnancy are both associated with offspring cardiac structure in childhood, but these associations seem to be fully explained by childhood body mass index.

Ventricular function and cardiac reserve in contemporary Fontan patients.

BACKGROUND/OBJECTIVE: Total cavopulmonary connection (TCPC) has been the preferred treatment for patients with univentricular hearts. Current TCPC-techniques are the intra-atrial lateral tunnel (ILT) and the extracardiac conduit (ECC). We aimed to determine ventricular function during rest and stress, and to compare results for both techniques and for left (LV) versus right ventricular (RV) dominance. METHODS: 99 patients, aged 12.5 ± 4.0 years underwent echocardiography and magnetic resonance imaging (MRI), and 69 patients underwent stress MRI. RESULTS: Echocardiography showed impaired systolic and diastolic function. MRI parameters were comparable between ILT and ECC at rest. During dobutamine there was a decrease in end-diastolic volume (EDVi) (91 ± 21 vs. 80 ± 20 ml/m(2) p<0.001). Ejection fraction (EF) and cardiac index (CI) during dobutamine were lower for ILT patients (59 ± 11 (ILT) vs. 64 ± 7% (ECC), p=0.027 and 4.2 ± 1.0 (ILT) vs. 4.9 ± 1.0L/min/m(2) (ECC), p=0.006), whereas other parameters were comparable. TEI-index was higher in ILT-patients (0.72 ± 0.27 (ILT) vs. 0.56 ± 0.22 (ECC), p=0.002). Diastolic function was frequently impaired in patients with a dominant RV (67% (RV) vs. 39% (LV), p=0.011). Patients with dominant LV's had smaller end-systolic volume (ESVi) (40 ± 13 (LV) vs. 47 ± 16 (RV) ml/m(2), p=0.030) and higher EF (55 ± 8 (LV) vs. 49 ± 9 ml/m(2) (RV), p=0.001) and contractility (2.3 ± 0.8 (LV) vs. 1.9 ± 0.7 mmHg/ml/m(2) (RV), p=0.050) during rest and higher EF during dobutamine (63 ± 8 (LV) vs. 58 ± 10 ml/m(2) (RV), p=0.043). CONCLUSION: Ventricular function is relatively well preserved in modern-day Fontan patients. With dobutamine stress there is a decrease in EDVi. ECC patients have higher CI and EF during stress. Patients with a dominant RV have lower systolic, including impaired contractility, and diastolic function.

Indications for cardiovascular magnetic resonance in children with congenital and acquired heart disease: an expert consensus paper of the Imaging Working Group of the AEPC and the Cardiovascular Magnetic Resonance Section of the EACVI.

This article provides expert opinion on the use of cardiovascular magnetic resonance (CMR) in young patients with congenital heart disease (CHD) and in specific clinical situations. As peculiar challenges apply to imaging children, paediatric aspects are repeatedly discussed. The first section of the paper addresses settings and techniques, including the basic sequences used in paediatric CMR, safety, and sedation. In the second section, the indication, application, and clinical relevance of CMR in the most frequent CHD are discussed in detail. In the current era of multimodality imaging, the strengths of CMR are compared with other imaging modalities. At the end of each chapter, a brief summary with expert consensus key points is provided. The recommendations provided are strongly clinically oriented. The paper addresses not only imagers performing CMR, but also clinical cardiologists who want to know which information can be obtained by CMR and how to integrate it in clinical decision-making.

Indications for cardiovascular magnetic resonance in children with congenital and acquired heart disease: an expert consensus paper of the Imaging Working Group of the AEPC and the Cardiovascular Magnetic Resonance Section of the EACVI.

This article provides expert opinion on the use of cardiovascular magnetic resonance (CMR) in young patients with congenital heart disease (CHD) and in specific clinical situations. As peculiar challenges apply to imaging children, paediatric aspects are repeatedly discussed. The first section of the paper addresses settings and techniques, including the basic sequences used in paediatric CMR, safety, and sedation. In the second section, the indication, application, and clinical relevance of CMR in the most frequent CHD are discussed in detail. In the current era of multimodality imaging, the strengths of CMR are compared with other imaging modalities. At the end of each chapter, a brief summary with expert consensus key points is provided. The recommendations provided are strongly clinically oriented. The paper addresses not only imagers performing CMR, but also clinical cardiologists who want to know which information can be obtained by CMR and how to integrate it in clinical decision-making.

The effect of exercise training on cardiac remodelling in children and young adults with corrected tetralogy of Fallot or Fontan circulation: a randomized controlled trial.

BACKGROUND: Exercise can improve physical fitness in children and adults with congenital heart disease. We hypothesized that exercise training would not lead to adverse cardiac remodelling in this population. METHODS AND RESULTS: This multi-centre randomized controlled trial included children and young adults (10 to 25 years) with either corrected tetralogy of Fallot or Fontan circulation. The exercise-group was enrolled in a 12 week standardized aerobic dynamic exercise training program. The control-group continued their life-style and received care as usual. Both groups underwent cardiopulmonary exercise testing, cardiac magnetic resonance imaging (MRI), echocardiography and neurohormonal assessment, within 2 weeks before and 2 weeks after the intervention period. Fifty-six patients were randomized to the exercise-group and 37 to the control-group. We assessed changes between the pre- and the post-intervention period for the exercise group compared to the changes in the control-group. Peak load increased significantly in the exercise-group compared to the control-group (exercise-group 6.9 ± 11.8 W; control-group 0.8 ± 13.9 W; p=0.047). There were no adverse events linked to the study. Ventricular systolic parameters, cardiac dimensions and neurohormonal markers during follow-up did not change in patients allocated to the exercise-group and control-group. Although there were some isolated minor changes in inflow parameters, there was no consistent pattern of changes, indicating a lack of true change in the diastolic function. CONCLUSION: We demonstrated that no clinically relevant adverse cardiac remodelling occurred after 12 weeks of exercise training in patients with either corrected tetralogy of Fallot or Fontan circulation. CLINICAL TRIAL REGISTRATION: www.trialregister.nl, identification NTR2731.

Cardiovascular diseases in grandparents and the risk of congenital heart diseases in grandchildren.

Hyperglycemia, dyslipidemia and hyperhomocysteinemia are associated with both adult cardiovascular disease (CVD) and having a child with a congenital heart disease (CHD). We investigated associations between CVD in grandparents and the risk of CHD in grandchildren. In a case-control family study, we obtained detailed questionnaire information on CVD and CHD in 247 families with a CHD child and 203 families without a CHD child. Grandparents with CVD or intermittent claudication (IC) were significantly associated with an increased risk for CHD in grandchildren [OR 1.39 (95% CI 1.03-1.89) and OR 2.77 (95% CI 1.02-7.56), respectively]. The risk of CHD grandchildren was particularly increased in paternal grandfathers with CVD [OR 1.85 (95% CI 1.01-3.37)]. Overall, having a grandparent with CVD increased the risk for CHD in the grandchild by 1.65 (95% CI 1.12-2.41). After adjustment for potential maternal confounders, this risk was 1.44 (95% CI 0.94-2.21). Having two or more grandparents with CVD was associated with an approximately threefold risk for CHD grandchildren [OR adjusted 2.72 (95% CI 1.08-6.89)]. Our data suggest that CVD and IC in grandparents are associated with an increased risk of having a CHD grandchild. These first findings may be explained by shared causality of derangements in metabolic pathways and are in line with the fetal origins of health and disease.

Systematic review of the effects of physical exercise training programmes in children and young adults with congenital heart disease.

BACKGROUND: Most patients with congenital heart disease (ConHD) do not perform regular physical exercise. Consensus reports have stated that exercise should be encouraged and regularly performed in these patients, but this is not common practise. We reviewed the literature on actual evidence for either negative or positive effects of physical exercise training programmes in children and young adults with ConHD. METHODS: Using the Medline database, we systematically searched for articles on physical exercise training programmes in ConHD. RESULTS: A total of 31 articles met all inclusion criteria; in total, 621 subjects (age range 4 to 45 years) were included. Most studies used training programmes with a duration of 12 weeks. On average, the number of training sessions was 3 times per week. In 12 studies, training intensity was set at a percentage of peak heart rate. Outcome measures reported were PeakVO2, activity levels and muscle strength. Twenty-three studies (72%) found a significant positive change in the main outcome measure after the physical exercise training period. None of the studies reported negative findings related to physical exercise training in ConHD. Cardiac effects have hardly been studied. CONCLUSION: In most studies, participation in a physical exercise training programme was safe and improved fitness in children and young adults with ConHD. We recommend that patients with ConHD participate in physical exercise training. Cardiac effects need to be studied more extensively.