Guidelines recommend screening for psychiatric co-morbidities in patients with congenital heart defects alongside cardiac outpatient follow-ups. These recommendations are not implemented in Denmark. This study aimed to investigate the psychiatric co-morbidities in children and adolescents with Fontan circulation in Denmark and to evaluate the feasibility of an online screening measure for psychiatric disorders.

Children, adolescents, and their families answered the Development and Well-Being Assessment questionnaire and a questionnaire about received help online. Development and Well-Being Assessment ratings present psychiatric diagnoses in accordance with ICD-10 and DSM-5. Parent-reported received psychiatric help is also presented. Feasibility data are reported as participation rate (completed Development and Well-Being Assessments) and parental/adolescent acceptability from the feasibility questionnaire.

The participation rate was 27%. Of the participating children and adolescents, 53% (ICD-10)/59% (DSM-5) met full diagnostic criteria for at least one psychiatric diagnosis. Of these, 50% had not received any psychiatric or psychological help. Only 12% of participants had an a priori psychiatric diagnosis.

We found that a large proportion of children and adolescents with Fontan circulation are underdiagnosed and undertreated for psychiatric disorders. The results from our study emphasise the need for psychiatric screening in this patient group. Development and Well-Being Assessment may be too comprehensive for online electronic screening in children and adolescents with CHD.

Tetralogy of Fallot patients face an elevated risk of developing chylothorax and pleural effusions post-surgery. This patient group exhibits risk factors known to compromise the lymphatic system, such as elevated central venous pressure, pulmonary flow changes, and hypoxia. This study investigates the morphology and function of the lymphatic system in tetralogy of Fallot patients through lymphatic magnetic resonance imaging and near-infrared fluorescence imaging, respectively.

Post-repair tetralogy of Fallot patients aged 6–18 years were recruited, along with age and gender-matched controls. Magnetic resonance imaging was used to assess the morphology of the thoracic lymphatic vessels and the thoracic, while near-infrared fluorescence imaging was used to assess lymphatic activity utilising lymph rate, velocity, and pressure.

Nine patients and 10 controls were included. Echocardiography revealed that 2/3 of the patients had moderate-severe pulmonary regurgitation, while none displayed signs of elevated central venous pressure. Magnetic resonance imaging identified three patients with type 3 (out of 4 types) lymphatic abnormalities, while controls had none. The thoracic ducts showed severe (one patient) and moderate (one patient) tortuosity. Mean thoracic duct diameters were 3.3 mm ±1.1 in patients and 3.0 mm ± 0.8 in controls (p-value = 0.53). Near-infrared fluorescence imaging revealed no anomalous patterns.

Despite no presence of clinical lymphatic disease, 3/9 of the repaired tetralogy of Fallot patients exhibited lymphatic morphological abnormalities. The significance of these anomalies remains uncertain currently. Further research is needed to determine whether these lymphatic alterations in this patient cohort are a result of congenital malformations, haemodynamic shifts, or prenatal and early-life saturation levels.

An interatrial communication is present in most neonates. The majority are considered the “normal” patency of the oval foramen, while a minority are abnormal atrial septal defects. Differentiation between the two with transthoracic echocardiography may be challenging, and no generally accepted method of classification is presently available. We aimed to develop and determine the reliability of a new classification of interatrial communications in newborns.

An algorithm was developed based on echocardiographic criteria from 495 newborns (median age 11[8;13] days, 51.5% females). The algorithm defines three main categories: patency of the oval foramen, atrial septal defect, and no interatrial communication as well as several subtypes. We found an interatrial communication in 414 (83.6%) newborns. Of these, 386 (93.2%) were categorised as patency of the oval foramen and 28 (6.8%) as atrial septal defects.

Echocardiograms from another 50 newborns (median age 11[8;13] days, 36.0% female), reviewed by eight experts in paediatric echocardiography, were used to assess the inter- and intraobserver variation of classification of interatrial communications into patency of the oval foramen and atrial septal defect, with and without the use of the algorithm. Review with the algorithm gave a substantial interobserver agreement (kappa = 0.66), and an almost perfect intraobserver agreement (kappa = 0.82). Without the use of the algorithm, the interobserver agreement between experienced paediatric cardiologists was low (kappa = 0.20).

A new algorithm for echocardiographic classification of interatrial communications in newborns produced almost perfect intraobserver and substantial interobserver agreement. The algorithm may prove useful in both research and clinical practice.

Adults with simple congenital heart defects (CHD) have increased risk of neurodevelopmental challenges including executive dysfunction. It is unknown if the executive dysfunction is universal or if it is driven by dysfunction in specific clinical subscales and how it might affect psychosocial aspects of everyday life.

The self-reported and informant-reported executive function of adults with an average age of 26 ± 5 (range 18–41) who underwent childhood surgery for atrial septal defects (n = 34) or ventricular septal defects (n = 32) and matched controls (n = 40) were evaluated using the Behavior Rating Inventory of Executive Functions - Adult version (BRIEF-A).

The CHD group reported having more executive dysfunction than controls in all BRIEF-A clinical subscales (p < 0.020) and more than their informants reported on their behalf (p < 0.006). The CHD group had received three times more special teaching (44% compared to 16%) and pedagogical psychological counselling (14% compared to none) and had a three times higher occurrence of psychiatric disorders than controls (33% compared to 11%). Lower educational levels and psychiatric disorders were associated with higher BRIEF-A scores (p < 0.03).

Adults operated for septal defects in childhood report more challenges with all aspects of the executive functions than controls and more than relatives are aware of.

The objective of this study was to investigate changes in serum biomarkers of acute brain injury, including white matter and astrocyte injury during chronic foetal hypoxaemia. We have previously shown histopathological changes in myelination and neuronal density in fetuses with chronic foetal hypoxaemia at a level consistent with CHD.

Mid-gestation foetal sheep (110 ± 3 days gestation) were cannulated and attached to a pumpless, low-resistance oxygenator circuit, and incubated in a sterile fluid environment mimicking the intrauterine environment. Fetuses were maintained with an oxygen delivery of 20–25 ml/kg/min (normoxemia) or 14–16 ml/kg/min (hypoxaemia). Myelin Basic Protein and Glial Fibrillary Acidic Protein serum levels in the two groups were assessed by ELISA at baseline and at 7, 14, and 21 days of support.

Based on overlapping 95% confidence intervals, there were no statistically significant differences in either Myelin Basic Protein or Glial Fibrillary Acidic Protein serum levels between the normoxemic and hypoxemic groups, at any time point. No statistically significant correlations were observed between oxygen delivery and levels of Myelin Basic Protein and Glial Fibrillary Acidic Protein.

Chronic foetal hypoxaemia during mid-gestation is not associated with elevated serum levels of acute white matter (Myelin Basic Protein) or astrocyte injury (Glial Fibrillary Acidic Protein), in this model. In conjunction with our previously reported findings, our data support the hypothesis that the brain dysmaturity with impaired myelination found in fetuses with chronic hypoxaemia is caused by disruption of normal developmental pathways rather than by direct cellular injury.

To compare early neurocognitive development in children born with and without isolated CHD using the Bayley Scales of Infant and Toddler Development (3rd edition) and the Ages and Stages Questionnaire (3rd edition).

Recruitment took place before birth. Women expecting fetuses with and without CHD causing disturbances in the flow of oxygenated blood to the fetal brain were included in a prospective cohort study comprising fetal MRI (previously published) and neurodevelopmental follow-up. We now present the 18- and 36-month neurodevelopmental follow-up using the Bayley Scales according to age and the 6-month-above-age Ages and Stages Questionnaire in 15 children with and 27 children without CHD.

Children with CHD had, compared with the children without CHD, an increased risk of scoring ≤ 100 in the Bayley Scales cognition category at 18 and 36 -months; relative risk 1.7 (95% confidence interval (CI): 1.0–2.8) and 3.1 (CI: 1.2–7.5), respectively. They also achieved lower scores in the 6-month-above-age Ages and Stages Questionnaires (24 and 42 months) communication; mean z-score difference −0.72 (CI: −1.4; −0.1) and −1.06 (CI: −1.8; −0.3) and gross motor; mean z-score difference: −0.87 (CI: −1.7; −0.1) and −1.22 (CI: −2.4; −0.02) categories.

The children with CHD achieved lower scores in the Bayley Scales cognition category and the Ages and Stages Questionnaire communication and gross motor categories possibly indicative of early neurodevelopmental deficiencies. We recommend early screening and monitoring for neurodevelopmental delays in children with CHD in order to improve further neurodevelopment and educational achievements.

Many children born with congenital heart defects are faced with cognitive deficits and psychological challenges later in life. The mechanisms behind are suggested to be multifactorial and are explained as an interplay between innate and modifiable risk factors. The aim was to assess whether there is a relationship between mean arterial pressure during surgery of a septal defect in infancy or early childhood and intelligence quotient scores in adulthood.

In a retrospective study, patients were included if they underwent surgical closure of a ventricular septal defect or an atrial septal defect in childhood between 1988 and 2002. Every patient completed an intelligence assessment upon inclusion, 14–27 years after surgery, using the Wechsler Adult Intelligence Scale Version IV.

A total of 58 patients met the eligibility criteria and were included in the analyses. No statistically significant correlation was found between blood pressure during cardiopulmonary bypass and intelligence quotient scores in adulthood (r = 0.138; 95% CI−0.133–0.389). Although amongst patients with mean arterial pressure < 40 mmHg during cardiopulmonary bypass, intelligence quotient scores were significantly lower (91.4; 95% CI 86.9–95.9) compared to those with mean arterial pressure > 40 mmHg (99.8; 95% CI 94.7–104.9).

Mean arterial pressure during surgery of ventricular septal defects or atrial septal defects in childhood does not correlate linearly with intelligence quotient scores in adulthood. Although there may exist a specific cut-off value at which low blood pressure becomes harmful. Larger studies are warranted in order to confirm this, as it holds the potential of partly relieving CHD patients of their cognitive deficits.

To determine the prevalence of pacemaker and conduction disturbances in patients with atrial septal defects.

All patients with an atrial septal defect born before 1994 were identified in the Danish National Patient Registry, and 297 patients were analysed for atrioventricular block, bradycardia, right bundle branch block, left anterior fascicular block, left posterior fascicular block, pacemaker, and mortality. Our results were compared with pre-existing data from a healthy background population. Further, outcomes were compared between patients with open atrial septal defects and atrial septal defects closed by surgery or transcatheter.

Most frequent findings were incomplete right bundle branch block (40.1%), left anterior fascicular block (3.7%), atrioventricular block (3.7%), and pacemaker (3.7%). Average age at pacemaker implantation was 32 years. Patients with defects closed surgically or by transcatheter had an increased prevalence of atrioventricular block (p < 0.01), incomplete right bundle branch block (p < 0.01), and left anterior fascicular block (p = 0.02) when compared to patients with unclosed atrial septal defects. At age above 25 years, there was a considerably higher prevalence of atrioventricular block (9.4% versus 0.1%) and complete right bundle branch block (1.9% versus 0.4%) when compared to the background cohorts.

Patients with atrial septal defects have a considerably higher prevalence of conduction abnormalities when compared to the background population. Patients with surgically or transcatheter closed atrial septal defects demonstrated a higher demand for pacemaker and a higher prevalence of atrioventricular block, incomplete right bundle branch block, and left anterior fascicular block when compared to patients with unclosed atrial septal defects.

Clinical studies have revealed decreased exercise capacity in adults with small, unrepaired ventricular septal defects. Increasing shunt ratio and growing incompetence of the aortic and pulmonary valve with retrograde flow during exercise have been proposed as reasons for the previously found reduced exercise parameters. With MRI, haemodynamic shunt properties were measured during exercise in ventricular septal defects.

Patients with small, unrepaired ventricular septal defects and healthy peers were examined with MRI during exercise. Quantitative flow scans measured blood flow through ascending aorta and pulmonary artery. Scans were analysed post hoc where cardiac index, retrograde flows, and shunt ratio were determined.

In total, 32 patients (26 ± 6 years) and 28 controls (27 ± 5 years) were included. The shunt ratio was 1.2 ± 0.2 at rest and decreased to 1.0 ± 0.2 at peak exercise, p < 0.01. Aortic cardiac index was lower at peak exercise in patients (7.5 ± 2 L/minute/m2) compared with controls (9.0±2L l/minute/m2), p<0.01. Aortic and pulmonary retrograde flow was larger in patients during exercise, p < 0.01. Positive correlation was demonstrated between aortic cardiac index at peak exercise and previously established exercise capacity for all patients (r = 0.5, p < 0.01).

Small, unrepaired ventricular septal defects revealed declining shunt ratio with increasing exercise and lower aortic cardiac index. Patients demonstrated larger retrograde flow both through the pulmonary artery and the aorta during exercise compared with controls. In conclusion, adults with unrepaired ventricular septal defects redistribute blood flow during exercise probably secondary to a more fixed pulmonary vascular resistance compared with age-matched peers.

Recent studies have demonstrated that surgical ventricular septal defect closure in childhood is associated with reduced functional capacity and disruption of the right ventricular force–frequency relationship during exercise. To further describe long-term cardiac function, we performed a non-invasive assessment of cardiac index during exercise in adults having undergone surgery for ventricular septal defect in early childhood.

A total of 20 patients (surgical age 2.1±1.4 years, age at examination 22.1±2.2 years) and 20 healthy, matched controls (23.4±2.1 years at examination) underwent continuous supine bicycle ergometry during MRI. Their blood flow was recorded in the ascending aorta and the pulmonary trunk at increasing exercise levels. Cardiac index, retrograde flow, and vessel diameters were determined by blinded, post hoc analyses.

The patient group had normal cardiac index at rest (2.9±0.7 L/minute/m2), which was comparable with that of the controls (3.0±0.6 L/minute/m2); however, they had a lower increase in cardiac index during exercise (reaching 7.3±1.3 L/minute/m2 at submaximal exercise) compared with controls (8.2±1.2 L/minute/m2), p<0.05. Patients had a significantly higher ascending aorta retrograde flow than controls at rest and throughout exercise. In the pulmonary artery, the retrograde flow was minimal at rest in both groups, but increased significantly in patients during exercise compared with controls.

Young adults with a surgically closed ventricular septal defect have a reduced cardiac index during exercise compared with healthy, young adults. The impaired cardiac index appears to be related to an increasing retrograde flow in the pulmonary artery with progressive exertion.

Surgical correction was the treatment of choice for pulmonary stenosis until three decades ago, when balloon valvuloplasty was implemented. The natural history of surgically relieved pulmonary stenosis has been considered benign but is actually unknown, as is the need for re-intervention.

The objective of this study was to investigate the morbidity and mortality of patients with surgically treated pulmonary stenosis operated at Aarhus University Hospital between 1957 and 2000.

The total study population included 80 patients. In-hospital mortality was 2/80 (2.5%), and an additional four patients died after hospital discharge; therefore, the long-term mortality was 5%. The maximum follow-up period was 57 years, with a median of 33 years. In all, 16 patients (20%) required at least one re-intervention. Pulmonary valve replacement due to pulmonary regurgitation was the most common re-intervention (67%). Freedom from re-intervention decreased >20 years after the initial repair. In addition, 45% of patients had moderate/severe pulmonary regurgitation, 38% had some degree of right ventricular dilatation, and 40% had some degree of tricuspid regurgitation, which did not require re-intervention at the present stage.

Surgical relief for pulmonary stenosis is efficient in relieving outflow obstruction; however, this efficiency is achieved at the cost of pulmonary regurgitation, leading to right ventricular dilatation and tricuspid regurgitation. When required, pulmonary valve replacement is performed most frequently >20 years after the initial surgery. Lifelong follow-up of patients treated surgically for pulmonary stenosis is emphasised in this group of patients, who might otherwise consider themselves cured.

Ventricular septal defects are normally closed in early childhood, and post-surgically the patients are considered as healthy and fit as their peers. However, data are inconsistent. We exercise-tested a cohort of ventricular septal defect-operated patients and a group of matched controls to evaluate long-term physical fitness.

Cardiopulmonary exercise capacity was tested on an ergometer cycle in 30 patients and 30 healthy age and gender-matched controls. Pulmonary ventilation and gas exchange were simultaneously measured breath-by-breath with Jaeger MasterScreen CPX® (CareFusion, San Diego, United States of America). During the test session, respiratory gas exchange was measured along with heart rate, blood pressure, and electrocardiogram. The endpoints were peak oxygen uptake, maximal workload, and ventilatory anaerobic threshold. The International Physical Activity Questionnaire and the SF-36 were applied for Health-Related Quality-of-Life assessment.

Ventricular septal defect-operated adults had a markedly lower peak oxygen uptake: mean 38.0(±8.2 ml O2/kg/minute) versus 47.9(±6.5 ml O2/kg/minute) in controls, p<0.01. Furthermore, ventilatory anaerobic threshold was impaired in ventricular septal defect patients: mean 25.3(±7.8 ml O2/kg/minute) versus 35.2(±7.7 ml O2/kg/minute) in controls, p<0.01. Maximal workload was reduced: mean 3.3(±0.7 W/kg) versus 4.0(±0.5 W/kg) in the control group, p<0.01. Lastly, ventricular septal defect patients had a significantly lower peak heart rate: mean 182(±8.8 beats/minute) versus 188(±9.0 beats/minute) in controls, p=0.03. Regarding Health-Related Quality of Life, the ventricular septal defect group had significantly lower scores in physical functioning, role physical, and social functioning.

Young adults with a surgically closed ventricular septal defect had a markedly reduced cardiopulmonary exercise capacity and a lower peak heart rate compared with controls.

Chronic pain is common after sternotomy in adults with reported prevalence rates of 20–50%. So far, no studies have examined whether children develop chronic pain after sternotomy.

Postal questionnaires were sent to 171 children 10–60 months after undergoing cardiac surgery via sternotomy at the age of 0–12 years. The children were asked to recall the intensity and duration of their post-operative pain, if necessary with the help from their parents, and to describe the intensity and character of any present pain. Another group of 13 children underwent quantitative sensory testing of the scar area 3 months after sternotomy.

A total of 121 children, median (range) age 7.7 (4.2–16.9) years, answered the questionnaire. Their age at the time of surgery was median (range) 3.8 (0–12.9) years, and the follow-up period was median (range) 4 (0.8–5.1) years. In all, 26 children (21%) reported present pain and/or pain within the last week located in the scar area; in 12 (46%) out of the 26 children, the intensity was ≥4 on a numeric rating scale (0–10). Quantitative sensory testing of the scar area revealed sensory abnormalities – pinprick hyperalgesia and brush and cold allodynia – in 10 out of 13 children.

Chronic pain after cardiac surgery via sternotomy in children is a problem that should not be neglected. The pain is likely to have a neuropathic component as suggested by the sensory abnormalities demonstrated by quantitative sensory testing.

We aimed to assess cancer risk in congenital heart defect patients, with and without Down's syndrome, compared with the general population.

We identified all patients born and diagnosed with congenital heart defects from 1977 to 2008 using the Danish National Registry of Patients, covering all Danish hospitals. We compared cancer incidence in the congenital heart defect cohort with that expected in the general population (∼5.5 million) using the Danish Cancer Registry, and computed age- and gender-standardised incidence ratios.

We identified 15,905 congenital heart defect patients, contributing a total of 151,172 person-years at risk; the maximum length of follow-up was 31 years (median 8 years). In all, 53 patients were diagnosed with cancer, including 30 female and 23 male patients (standardised incidence ratio = 1.63; 95% confidence interval: 1.22–2.13). Risks were increased for leukaemia, brain tumours, and basal cell carcinoma. After excluding 801 patients with Down's syndrome, the standardised incidence ratio was 1.19 (95% confidence interval: 0.84–1.64). In the subgroup of 5660 non-Down's syndrome patients undergoing cardiac surgery or catheter-based interventions, the standardised incidence ratio was 1.45 (95% confidence interval: 0.86–2.29).

The overall risk of cancer among congenital heart defect patients without Down's syndrome was not statistically significantly elevated. Cancer risk in the congenital heart defect cohort as a whole, including patients with Down's syndrome, was increased compared with the general population, although the absolute risk was low. Studies with longer follow-up and more information on radiation doses are needed to further examine a potential cancer risk associated with diagnostic radiation exposure.

Little is known about the quality of life, health, family, education, and employment status among adult men with repaired tetralogy of Fallot.

A total of 68 men who underwent repair of tetralogy of Fallot between 1971 and 1991 were studied. Fifty-three patients answered the SF-36 health survey and additional questions regarding offspring, education, and employment status. The men with repaired tetralogy of Fallot were compared with 32 healthy men and 40 women who also underwent repair of tetralogy of Fallot in the same period.

The patients scored lower than healthy men in the SF-36 categories physical functioning, general health, and physical component summary. There were no statistically significant differences in the scores from male and female patients except a lower score in bodily pain among women. Educational level for men operated for tetralogy of Fallot was similar to the general male population, whereas fewer were employed and more were retired, undergoing rehabilitation or receiving social benefits. The reproduction rate was lower compared with the general population (0.65 versus 1.02 children per man) but relatively higher than the rate among women with tetralogy of Fallot (0.88 versus 1.84 children per woman). The risk of having a child with congenital heart disease was 8.3%.

Men operated for tetralogy of Fallot have good quality of life and educational status. They start a family, although their reproduction rate is two-thirds that of the general population. The risk of having a child with congenital heart disease is higher compared with the background population. The overall quality of life is similar for men and women operated for tetralogy of Fallot.

Congenital heart defect patients may experience neurodevelopmental impairment. We investigated their educational attainments from basic schooling to higher education.

Using administrative databases, we identified all Danish patients with a cardiac defect diagnosis born from 1 January, 1977 to 1 January, 1991 and alive at age 13 years. As a comparison cohort, we randomly sampled 10 persons per patient. We obtained information on educational attainment from Denmark's Database for Labour Market Research. The study population was followed until achievement of educational levels, death, emigration, or 1 January, 2006. We estimated the hazard ratio of attaining given educational levels, conditional on completing preceding levels, using discrete-time Cox regression and adjusting for socio-economic factors. Analyses were repeated for a sub-cohort of patients and controls born at term and without extracardiac defects or chromosomal anomalies.

We identified 2986 patients. Their probability of completing compulsory basic schooling was approximately 10% lower than that of control individuals (adjusted hazard ratio = 0.79, ranged from 0.75 to 0.82 0.79; 95% confidence interval: 0.75–0.82). Their subsequent probability of completing secondary school was lower than that of the controls, both for all patients (adjusted hazard ratio = 0.74; 95% confidence interval: 0.69–0.80) and for the sub-cohort (adjusted hazard ratio = 0.80; 95% confidence interval: 0.73–0.86). The probability of attaining a higher degree, conditional on completion of youth education, was affected both for all patients (adjusted hazard ratio = 0.88; 95% confidence interval: 0.76–1.01) and for the sub-cohort (adjusted hazard ratio = 0.92; 95% confidence interval: 0.79–1.07).

The probability of educational attainment was reduced among long-term congenital heart defect survivors.