Processing Speed Partially Mediates Executive Function Impairments in Adolescents with Congenital Heart Disease: Results from a Prospective Cohort Study.

OBJECTIVE: To assess processing speed, fine motor function, attention, and executive function (EF) impairments in adolescents with complex congenital heart disease (CHD) who underwent open-heart surgery during infancy. STUDY DESIGN: We administered a comprehensive neuropsychological test battery evaluating 5 EF domains: working memory, inhibition, cognitive flexibility, fluency, and planning and primary neurodevelopmental processes (PNPs): processing speed, fine motor function, and attention. The sample included 100 adolescents with complex CHD from a previous University Children's Hospital Zurich study, with 104 healthy controls for comparison. We generated scores for each EF domain and computed an EF summary score. Group comparisons and associations were analyzed with multiple regressions accounting for parental education. Mediation analysis explored how PNPs mediate the effect between a CHD diagnosis and EF. RESULTS: In adolescents with complex CHD, all EF domains and the EF summary score were impaired (ß = 0.20 to 0.37, all P < .05). Furthermore, they exhibited slower processing speed (ß = 0.27, P < .01) than healthy controls, with no differences in attention (ß = -0.07, P = .34) and fine motor function (ß = 0.08, P = .34). Processing speed showed a strong association with the EF summary score (ß = 0.60, P < .001) and partially mediated the relationship between CHD diagnosis and the EF summary score (ß = 0.37, 95% CI [0.24, 0.50], P < .001). CONCLUSION: Adolescents with complex CHD show difficulties in EFs and processing speed. Notably, processing speed is strongly associated with EFs and partly accounts for EFs disparities between patients and healthy controls. Early detection and interventions for processing speed difficulties may improve EF outcomes in these patients.

Heart rate variability and cognitive functions in adolescents with complex congenital heart disease.

BACKGROUND: Heart Rate Variability (HRV) originates from the interplay between parasympathetic/sympathetic inputs to the heart, thus serving as an indicator of Autonomic Nervous System regulation. Prior research indicates that decreased HRV, marked by reduced autonomic balance, is related to poorer cognitive performance. While the population with congenital heart disease (CHD) show changes in HRV linked with the heart defect, the association between HRV and cognitive functions in CHD remains unexplored. METHODS: 46 adolescents with CHD who went through infant open-heart surgery and 64 healthy controls (50.9% males, 12.8 ± 1.4 years) underwent neurodevelopmental testing and photoplethysmograph acquisition. Group differences and associations with cognitive functions were analysed with linear regression. P values were FDR-corrected. RESULTS: Adolescents with CHD showed lower HRV (quantified by high-frequency power) compared to controls (p < 0.001). Lower HRV was correlated with worse executive function (ß = 0.24, p = 0.044) and lower IQ (ß = 0.26, p = 0.010) in the whole sample and with lower IQ (ß = 0.35, p = 0.014) in the CHD group. These associations were robust to confounders, including age, sex, and socioeconomic status. CONCLUSION: Our findings demonstrate an association between HRV and cognitive functions in adolescents with complex CHD. Early detection of alterations in HRV/autonomic regulation may help to identify children with CHD at risk for cognitive impairments. IMPACT: Adolescents with congenital heart disease (CHD) showed lower heart rate variability (HRV), indicating an imbalanced autonomic nervous system. Lower HRV was associated with lower IQ and executive function (EF) in the whole sample. The association between HRV and IQ was significantly stronger in CHD than in healthy controls. This study provides the first evidence of a link between altered HRV and cognitive impairments in the CHD population. Neurodevelopmental impairments seen in adolescents with CHD could be linked to their altered cardiac autonomic nervous activity, marked by low HRV.

The implementation of EMI-Heart, a family-tailored early motor intervention in infants with complex congenital heart disease, in practice: a feasibility RCT.

BACKGROUND: Children with congenital heart disease (CHD) who undergo open-heart surgery are at risk of developmental impairment, including motor delay, which contributes to parental concerns. Additionally, parents experience prolonged stress associated with their child's disease. There is a lack of early motor interventions in infants with CHD accounting for parental burdens. We developed a family-tailored early motor intervention (EMI-Heart), aiming to promote motor development in infants with CHD and family well-being. The primary aim was to evaluate the feasibility of the study design and the intervention. The secondary aim was to evaluate differences between the intervention and the control group in motor outcomes and family well-being at baseline (3-5 months), post-treatment (6-8 months), and at follow-up (12 months). METHOD: In this single-centre feasibility randomized control trial (RCT), infants with CHD after open-heart surgery without genetic or major neurological comorbidities were randomly allocated to EMI-Heart or the control group (standard of care). EMI-Heart's key elements promote postural functional activities and encourage parental sensitivity to infants' motor and behaviour cues. Infants assigned to EMI-Heart received nine sessions of early motor intervention at home, in the hospital, and online for a duration of 3 months by a paediatric physiotherapist. We performed descriptive statistics for feasibility and secondary outcomes. RESULTS: The recruitment rate was 59% (10/17), all participating families completed the study (10/10), and the intervention duration was 3.9 months (± 0.54), including nine intervention sessions per family. Median acceptability to parents was 3.9 (1 = not agree-4 = totally agree, Likert scale). The paediatric physiotherapist considered the intervention as feasible. The comparison of motor outcomes did not show differences between groups. However, we detected improved reliable change scores in family well-being outcomes for families of the intervention group compared to the controls. CONCLUSIONS: Our research indicates that EMI-Heart is a feasible intervention for infants with CHD after open-heart surgery. The intervention was highly acceptable both to parents and to the paediatric physiotherapist. Online treatment sessions offer a valuable alternative to home and hospital visits. This feasibility RCT provides a foundation for a future full trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCTT04666857. Registered 23.11.2020.

Stress Markers, Executive Functioning, and Resilience Among Early Adolescents With Complex Congenital Heart Disease.

Importance: Infants with complex congenital heart disease (cCHD) may experience prolonged and severe stress when undergoing open heart surgery. However, little is known about long-term stress and its role in neurodevelopmental impairments in this population. Objective: To investigate potential differences between early adolescents aged 10 to 15 years with cCHD and healthy controls in physiological stress markers by hair analysis, executive function (EF) performance, and resilience. Design, Setting, and Participants: This single-center, population-based case-control study was conducted at the University Children's Hospital Zurich, Switzerland. Patients with different types of cCHD who underwent cardiopulmonary bypass surgery during the first year of life and who did not have a genetic disorder were included in a prospective cohort study between 2004 and 2012. A total of 178 patients were eligible for assessment at ages 10 to 15 years. A control group of healthy term-born individuals was cross-sectionally recruited. Data assessment was between 2019 and 2021. Statistical analysis was performed from January to April 2023. Exposure: Patients with cCHD who underwent infant open heart surgery. Main Outcomes and Measures: Physiological stress markers were quantified by summing cortisol and cortisone concentrations measured with liquid chromatography with tandem mass spectrometry in a 3-centimeter hair strand. EFs were assessed with a neuropsychological test battery to produce an age-adjusted EF summary score. Resilience was assessed with a standardized self-report questionnaire. Results: The study included 100 patients with cCHD and 104 controls between 10 and 15 years of age (mean [SD] age, 13.3 [1.3] years); 110 (53.9%) were male and 94 (46.1%) were female. When adjusting for age, sex, and parental education, patients had significantly higher sums of hair cortisol and cortisone concentrations (ß, 0.28 [95% CI, 0.12 to 0.43]; P < .001) and lower EF scores (ß, -0.36 [95% CI, -0.49 to -0.23]; P < .001) than controls. There was no group difference in self-reported resilience (ß, -0.04 [95% CI, -0.23 to 0.12]; P = .63). A significant interaction effect between stress markers and EFs was found, indicating a stronger negative association in patients than controls (ß, -0.65 [95% CI, -1.15 to -0.15]; P = .01). The contrast effects were not significant in patients (ß, -0.21 [95% CI, -0.43 to -0.00]; P = .06) and controls (ß, 0.09 [95% CI, -0.11 to 0.30]; P = .38). Conclusions and Relevance: This case-control study provides evidence for altered physiological stress levels in adolescents with cCHD and an association with poorer EF. These results suggest that future studies are needed to better understand the neurobiological mechanisms and timing of alterations in the stress system and its role in neurodevelopment.

Possible effects of left pulmonary artery stenting in single ventricle patients on bronchial area, lung volume and lung function.

Background: Left pulmonary artery (LPA) stenting is often required in single ventricle (SV) patients. Due to their close anatomical relationship an LPA stent could potentially compress the left main bronchus (LMB). We assessed the impact of LPA stenting on bronchial size, pulmonary volumes, and lung function in a cohort of SV patients. Methods: Forty-nine patients underwent cardiovascular magnetic resonance (CMR) and 36 spirometry 11 (8-15) years after Fontan. All patients were free of respiratory symptoms. LPA stents were inserted in 17 (35%) patients at 8.8 (3.4-12.6) years. Area/shape of the main bronchi (n = 46) and lung volumes (n = 47) were calculated from CMR-ZTE images for each lung and transformed in right-to-left (r/l) ratio and indexed for BSA. The effect of early stent insertion (prior to stage III) was analyzed. Results: Patients with LPA stent had larger r/l ratio for main bronchus area (p < 0.001) and r/l ratio difference for lung volumes was slightly larger in patients with early stenting. A trend toward a deformation of LMB shape in patients with LPA stent and toward a higher prevalence of abnormal spirometry in patients with early stent implantation was observed. Conclusions: In this cohort of patients, early insertion of LPA stents seems to relate with smaller LMB sizes and a trend toward smaller left lung volume and higher prevalence of impaired lung function. Whether these findings are caused by the stent or, at least to a certain degree, present prior to the implantation needs to be verified.