Self- and informant-reported executive function in young adults operated for atrial or ventricular septal defects in childhood.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Long-term neurodevelopmental effects of intraoperative blood pressure during surgical closure of a septal defect in infancy or early childhood.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Disappearance of the shunt and lower cardiac index during exercise in small, unrepaired ventricular septal defects.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Biventricular morphology in adults born with a ventricular septal defect.

Ventricular septal defects - large, surgically closed or small, untreated - have demonstrated lower peak exercise capacity compared with healthy controls. The mechanisms behind these findings are not yet fully understood. Therefore, we evaluated biventricular morphology in adults with a ventricular septal defect using MRI. Adults with either childhood surgically closed or small, untreated ventricular septal defects and healthy controls underwent cine MRI for the evaluation of biventricular volumes and quantitative flow scans for measurement of stroke index. Scans were analysed post hoc in a blinded manner. In total, 20 operated patients (22±2 years) and 20 healthy controls (23±2 years) were included, along with 32 patients with small, unrepaired ventricular septal defects (26±6 years) and 28 controls (27±5 years). Operated patients demonstrated larger right ventricular end-diastolic volume index (103±20 ml/m2) compared with their controls (88±16 ml/m2), p=0.01. Heart rate and right ventricular stroke index did not differ between operated patients and controls. Patients with unrepaired ventricular septal defects revealed larger right ventricular end-diastolic volume index (105±17 ml/m2) compared with their controls (88±13 ml/m2), p<0.01. Furthermore, right ventricular stroke index was higher in unrepaired ventricular septal defects (53±12 ml/minute/m2) compared with controls (46±8 ml/minute/m2), p=0.02, with similar heart rates. Both patient groups' right ventricles were visually characterised by abundant coarse trabeculation. Positive correlations were demonstrated between right ventricular end-diastolic volume indices and peak exercise capacity in patients. Left ventricle measurements displayed no differences between groups. In conclusion, altered right ventricular morphology was demonstrated in adults 20 years after surgical ventricular septal defect repair and in adults with small, untreated ventricular septal defects.

Impaired cardiac output during exercise in adults operated for ventricular septal defect in childhood: a hitherto unrecognised pathophysiological response.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Self- and proxy-reported impaired social interaction in young adults with simple congenital heart defects.

Background: Simple Congenital Heart Defects such as septal defects constitute a large proportion of Congenital Heart Defects. New research has demonstrated more co-morbidities than previously thought. In particular, co-morbidities involving neurocognitive, psychiatric, and social difficulties have been described. Neurocognitive and psychiatric morbidities affect social interaction. Social interaction is important in everyday social life (education, work life, family life). In this study, we investigated social interaction through self- and proxy-answered Social Responsiveness Scale 2 (SRS-2) in young adults with simple Congenital Heart Defects and compared their social interaction profile to healthy matched controls. Methods: We included a total of 80 patients with either atrial or ventricular septal defect (age 26.6 years) and 38 heart-healthy, age, sex, and ISCED educational matched controls (age: 25.3 years). A close relative proxy from each participant took part in the study as well. All participants answered the Social Responsiveness Scale 2 (SRS-2) (n = 225). Our primary and secondary outcomes were the SRS-2 Total score and the SRS-2 sub-scores. Results: In the Congenital Heart Defects group, 31.3% had a Total score above 60 compared to 7.9% in the control group (p = 0.005, RR = 3.96). The participants with a septal defect had a higher Total score (52.5 vs. 45.5, p = 0.004), a higher Social Cognition sub-score (55.0 vs. 47.0, p = 0.0004), and a higher Social Motivation sub-score (50.0 vs. 45.0, p = 0.003) than the heart-healthy participants. We found no difference between the two groups regarding the sub-scores of Social Awareness and Social Communication. A multiple linear regression model showed that the variable that explained most of the variation in Total Score was having a previously diagnosed psychiatric disorder. Conclusion: We found that young adults with atrial or ventricular septal defects have a fourfold increased risk of social interaction difficulties compared to heart-healthy peers. They have a social interaction profile, with difficulties in social cognition and social motivation, and preserved social awareness and social communication. Psychiatric morbidity explained most of the variation in social interaction problems. As social difficulties and psychiatric morbidities are intertwined, social interaction difficulties could be an indication of already underlying psychiatric morbidities or a risk factor for future psychiatric morbidity.

Altered Cerebral Microstructure in Adults With Atrial Septal Defect and Ventricular Septal Defect Repaired in Childhood.

Background Delayed brain development, brain injury, and neurodevelopmental disabilities are commonly observed in infants operated for complex congenital heart defect. Our previous findings of poorer neurodevelopmental outcomes in individuals operated for simple congenital heart defects calls for further etiological clarification. Hence, we examined the microstructural tissue composition in cerebral cortex and subcortical structures in comparison to healthy controls and whether differences were associated with neurodevelopmental outcomes. Methods and Results Adults (n=62) who underwent surgical closure of an atrial septal defect (n=33) or a ventricular septal defect (n=29) in childhood and a group of healthy, matched controls (n=38) were enrolled. Brain diffusional kurtosis imaging and neuropsychological assessment were performed. Cortical and subcortical tissue microstructure were assessed using mean kurtosis tensor and mean diffusivity and compared between groups and tested for associations with neuropsychological outcomes. Alterations in microstructural tissue composition were found in the parietal, temporal, and occipital lobes in the congenital heart defects, with distinct mean kurtosis tensor cluster-specific changes in the right visual cortex (pericalcarine gyrus, P=0.002; occipital part of fusiform and lingual gyri, P=0.019). Altered microstructural tissue composition in the subcortical structures was uncovered in atrial septal defects but not in ventricular septal defects. Associations were found between altered cerebral microstructure and social recognition and executive function. Conclusions Children operated for simple congenital heart defects demonstrated altered microstructural tissue composition in the cerebral cortex and subcortical structures during adulthood when compared with healthy peers. Alterations in cerebral microstructural tissue composition were associated with poorer neuropsychological performance. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871881.

Hyperactivity and Inattention in Young Patients Born With an Atrial Septal or Ventricular Septal Defect.

Background: Patients with congenital heart defects have a well-established risk of neuropsychiatric comorbidities. Inattention and hyperactivity are three to four times more frequent in children with complex congenital heart defects. We have previously shown a higher burden of overall attention deficit/hyperactivity disorder (ADHD) symptoms in adults with simple congenital heart defects as well. However, it is unknown whether the higher burden of ADHD symptoms is mainly driven by hyperactivity, inattention, or both. Methods: The participants [simple congenital heart defect = 80 (26.6 years old), controls = 36 (25.3 years old)] and a close relative for each (n = 107) responded to the long version of the Conners' Adults ADHD Rating Scales questionnaire. Our primary and secondary outcomes are mean T-scores in the ADHD scores and symptom sub-scores. Results: Patients with simple congenital heart defects reported a higher mean T-score at all three DSM-IV ADHD scores (ADHD-combined: 52.8 vs. 44.9, p = 0.007, ADHD-inattention: 55.5 vs. 46.4, p = 0.002, and ADHD-hyperactivity: 49.4 vs. 44.0, p = 0.03) and in all four ADHD symptom sub-scores (inattention/memory problems: 50.3 vs. 44.2, p = 0.001, hyperactivity/restlessness: 49.7 vs. 45.9, p = 0.03, impulsivity/emotional lability: 50.0 vs. 41.3, p = 0.001, and self-esteem problems: 53.8 vs. 46.3, p = 0.003). The results were maintained after the removal of outliers (incongruent responses), albeit the hyperactivity/restlessness ADHD symptom sub-score lost significance. Self- and informant ratings differed significantly on the ADHD-inattention score for the congenital heart defect group, where informants rated the ADHD-inattention scores better than the congenital heart defect patients rated themselves. Conclusions: Patients with a simple congenital heart defect have a higher symptom burden across all ADHD scores and all symptom sub-scores. The higher burden of ADHD is driven by both inattention and hyperactivity symptoms, though the inattention symptoms seem more prominent. Close relatives were less aware of the inattention symptoms than the congenital heart defect patients themselves. Routine screening for ADHD symptoms may be warranted to facilitate adequate help and guidance as these symptoms are easily overlooked. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03871881.

Abnormal Left-Hemispheric Sulcal Patterns in Adults With Simple Congenital Heart Defects Repaired in Childhood.

Background Children operated on for a simple congenital heart defect (CHD) are at risk of neurodevelopmental abnormalities. Abnormal cortical development and folding have been observed in fetuses with CHD. We examined whether sulcal folding patterns in adults operated on for simple CHD in childhood differ from those of healthy controls, and whether such differences are associated with neuropsychological outcomes. Methods and Results Patients (mean age, 24.5 years) who underwent childhood surgery for isolated atrial septal defect (ASD; n=33) or ventricular septal defect (VSD; n=30) and healthy controls (n=37) were enrolled. Sulcal pattern similarity to healthy controls was determined using magnetic resonance imaging and looking at features of sulcal folds, their intersulcal relationships, and sulcal graph topology. The sulcal pattern similarity values were tested for associations with comprehensive neuropsychological scores. Patients with both ASD and VSD had decreased sulcal pattern similarity in the left hemisphere compared with controls. The differences were found in the left temporal lobe in the ASD group and in the whole left hemisphere in the VSD group (P=0.033 and P=0.039, respectively). The extent of abnormal left hemispheric sulcal pattern similarity was associated with worse neuropsychological scores (intelligence, executive function, and visuospatial abilities) in the VSD group, and special educational support in the ASD group. Conclusions Adults who underwent surgery for simple CHD in childhood display altered left hemisphere sulcal folding patterns, commensurate with neuropsychological scores for patients with VSD and special educational support for ASD. This may indicate that simple CHD affects early brain development. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871881.

Neuropsychological Status and Structural Brain Imaging in Adults With Simple Congenital Heart Defects Closed in Childhood.

Background Neurodevelopmental impairments are common in survivors of complex congenital heart defects (CHD). We report neuropsychological and brain imaging assessments in adults operated for isolated septal defects. Methods and Results Patients (mean age 25.6 yrs) who underwent childhood surgery for isolated atrial septal defect (n=34) or ventricular septal defect (n=32), and healthy matched peers (n=40), underwent a standard battery of neuropsychological tests and a 3.0T brain magnetic resonance imaging scan. Patient intelligence was affected with lower scores on Full-Scale intelligence quotient (P<0.001), Verbal Comprehension (P<0.001), Perceptual Reasoning (P=0.007), and Working Memory (P<0.001) compared with controls. Also, the CHD group had poorer visuospatial abilities (Immediate Recall, P=0.033; Delayed Recall, P=0.018), verbal memory (Trial 1, P=0.015; Total Learning, P<0.001; Delayed Recall, P=0.007), executive function (Executive Composite Score, P<0.001), and social recognition (Reading the Mind in the Eyes Test, P=0.002) compared with controls. Self-reported levels of executive dysfunction, attention deficits and hyperactivity behavior, and social cognition dysfunction were higher in the CHD group compared with population means and controls. We found similar global and regional morphometric brain volumes and a similar frequency of brain magnetic resonance imaging abnormalities in the 2 groups. The CHD group had a high occurrence of psychiatric disease and a larger need for special teaching during school age. Conclusions Children operated for simple CHD demonstrate poorer neurodevelopmental outcomes in adulthood when compared with healthy controls and expected population means. REGISTRATION URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT03871881.

Dynamic bicycle exercise to assess cardiac output at multiple exercise levels during magnetic resonance imaging.

PURPOSE: The aim was to establish a method for performing dynamic exercise during magnetic resonance imaging (MRI) using a slowly increasing workload protocol. METHODS: An ergometer bicycle with a step-wise, exercise protocol was used. Real-time phase-contrast MRI images of the aorta were obtained at each exercise step. RESULTS: In total, 40 participants completed the exercise protocol to reach a mean maximum cardiac output of 13.7±3.7l/min and a heart rate of 150±16beats/min at the highest exercise level. Less than 1% of scans were discarded due to poor quality. CONCLUSIONS: Dynamic, high intensity exercise is feasible during MRI.

Does functional capacity depend on the size of the shunt? A prospective, cohort study of adults with small, unrepaired ventricular septal defects.

Objectives: Small ventricular septal defects (VSDs) are considered to have great prognoses and most remain unrepaired. However, we have recently demonstrated lower functional capacity in patients with small VSDs compared with healthy peers. Using magnetic resonance imaging scans, we determined whether the functional capacity was correlated to the size of the shunt. Methods: We included patients with unrepaired VSDs and healthy adults between 18 and 40 years of age in a prospective, cohort study. Functional capacity was previously determined using an incremental bicycle test, establishing peak oxygen uptake. Magnetic resonance imaging scans were performed using a 1.5-tesla Philips scanner. With electrocardiographically triggered flow measurements, we calculated mean cardiac output from the pulmonary trunk and ascending aorta as well as vessel diameters. Results: In total, 29 patients with unrepaired VSDs (26.5 ± 6 years) and 25 controls (26.9 ± 5 years) completed both studies. Previously measured peak oxygen uptake was nearly 20% lower in patients compared with controls (P = 0.002). All patients had shunt ratios below 1.5, with mean QpQs of 1.2 ± 0.1. When correlating shunt size to functional capacity, a negative correlation was found between the shunt ratio and peak oxygen uptake (r = −0.44, P = 0.020). Compared with controls, patients had increased forward and retrograde flow in the pulmonary trunk but comparable flows in the ascending aorta. Pulmonary diameter was also increased in patients (30.3 ± 4 mm) compared with controls (28.2 ± 3 mm; P = 0.041), whereas aortic dimensions were comparable. Conclusions: Our results demonstrate that, although small, unrepaired VSDs revealed reduced functional capacity that can be negatively correlated to the size of the shunt.