Efficacy of a Transition Program in Adolescents and Young Adults With Congenital Heart Disease: The TRANSITION-CHD Randomized Controlled Trial.

PURPOSE: Currently, nearly 90% of patients with congenital heart disease (CHD) reach adulthood in relatively good health. Structured transition programs have emerged to support adolescents and young adults in transitioning to adult care structures, improve their autonomy, and limit healthcare ruptures. The TRANSITION-CHD randomized controlled trial aimed to assess the impact of a transition program on health-related quality of life (HRQoL) in adolescents and young adults with CHD. METHODS: From January 2017 to February 2020, 200 subjects with a CHD, aged 13-25 years, were enrolled in a prospective, controlled, multicenter study and randomized in two balanced groups (transition program vs. standard of care). The primary outcome was the change in PedsQL self-reported HRQoL score between baseline and 12-month follow-up, using an intention-to-treat analysis. The secondary outcomes were the change in disease knowledge, physical health (cardiopulmonary fitness, physical activity), and mental health (anxiety, depression). RESULTS: The change in HRQoL differed significantly between the transition group and the control group (mean difference = 3.03, 95% confidence interval (CI) = [0.08; 5.98]; p = .044; effect size = 0.30), in favor of the intervention group. A significant increase was also observed in the self-reported psychosocial HRQoL (mean difference = 3.33, 95% CI = [0.01; 6.64]; p = .049; effect size = 0.29), in the proxy-reported physical HRQoL (mean difference = 9.18, 95% CI = [1.86; 16.51]; p = .015; effect size = 0.53), and in disease knowledge (mean difference = 3.13, 95% CI = [1.54; 4.72]; p < .001; effect size = 0.64). DISCUSSION: The TRANSITION-CHD program improved HRQoL and disease knowledge in adolescents and young adults with CHD, supporting the generalization and systematization of similar preventive interventions in pediatric and congenital cardiology.

Aerobic physical capacity and health-related quality of life in children with sickle cell disease.

BACKGROUND: Aerobic fitness is a predictor of cardiovascular health which correlates with health-related quality of life in the general population. The aim is to evaluate the aerobic capacity by cardiopulmonary exercise test (CPET) in children with sickle cell disease in comparison with healthy matched controls. METHODS: Controlled cross-sectional study. RESULTS: A total of 72 children (24 with sickle cell disease and 48 healthy controls), aged 6-17 years old were enrolled. Children with sickle cell disease had a poor aerobic capacity, with median VO2max Z-score values significantly lower than matched controls (-3.55[-4.68; -2.02] vs. 0.25[-0.22; 0.66], P < 0.01, respectively), and a high proportion of 92% children affected by an impaired aerobic capacity (VO2max Z-score < -1.64). The VO2max decrease was associated with the level of anemia, the existence of a homozygote HbS/S mutation, restrictive lung disease and health-related quality of life. CONCLUSION: Aerobic capacity is poor in children with sickle cell disease. VO2max decrease is associated with the level of anemia, the existence of a homozygote HbS/S mutation, lung function, and health-related quality of life. These results represent a signal in favor of early initiation of cardiac rehabilitation in patients with sickle cell disease. CLINICAL TRIALS: NCT05995743. IMPACT: Aerobic fitness is a predictor of cardiovascular health which correlates with health-related quality of life in the general population. Aerobic capacity (VO2max) is poor in children with sickle cell disease, despite the absence of any pattern of heart failure. VO2max decrease was associated with the level of anemia, the existence of a homozygote HbS/S mutation, restrictive lung disease, and health-related quality of life. These results are in favor of early initiation of cardiac rehabilitation in children with sickle cell disease.

Reference Values of Cardiopulmonary Exercise Test Parameters in the Contemporary Paediatric Population.

BACKGROUND: The evaluation of health status by cardiopulmonary exercise test (CPET) has shown increasing interest in the paediatric population. Our group recently established reference Z-score values for paediatric cycle ergometer VO2max, applicable to normal and extreme weights, from a cohort of 1141 healthy children. There are currently no validated reference values for the other CPET parameters in the paediatric population. This study aimed to establish, from the same cohort, reference Z-score values for the main paediatric cycle ergometer CPET parameters, apart from VO2max. RESULTS: In this cross-sectional study, 909 healthy children aged 5-18 years old underwent a CPET. Linear, quadratic, and polynomial mathematical regression equations were applied to identify the best CPET parameters Z-scores, according to anthropometric parameters (sex, age, height, weight, and BMI). This study provided Z-scores for maximal CPET parameters (heart rate, respiratory exchange ratio, workload, and oxygen pulse), submaximal CPET parameters (ventilatory anaerobic threshold, VE/VCO2 slope, and oxygen uptake efficiency slope), and maximum ventilatory CPET parameters (tidal volume, respiratory rate, breathing reserve, and ventilatory equivalent for CO2 and O2). CONCLUSIONS: This study defined paediatric reference Z-score values for the main cycle ergometer CPET parameters, in addition to the existing reference values for VO2max, applicable to children of normal and extreme weights. Providing Z-scores for CPET parameters in the paediatric population should be useful in the follow-up of children with various chronic diseases. Thus, new paediatric research fields are opening up, such as prognostic studies and clinical trials using cardiopulmonary fitness outcomes. Trial registration NCT04876209-Registered 6 May 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04876209 .

Use of new paediatric VO2max reference equations to evaluate aerobic fitness in overweight or obese children with congenital heart disease.

AIMS: Overweight and obesity in children with congenital heart disease (CHD) represent an alarming cardiovascular risk. Promotion of physical activity and cardiac rehabilitation in this population requires assessing the level of aerobic fitness (VO2max) by a cardiopulmonary exercise test (CPET). Nevertheless, the interpretation of CPET in overweight/obese children with CHD remains challenging as VO2max is affected by both the cardiac condition and the body mass index (BMI). The new paediatric VO2max  Z-score reference equations, based on a logarithmic function of VO2max, height and BMI, were applied to overweight/obese children with a CHD and compared with overweight/obese children without any other chronic condition. METHODS AND RESULTS: In this cross-sectional controlled study, 344 children with a BMI > 85th percentile underwent a CPET (54% boys; mean age 11.5 ± 3.1 years; 100 CHD; 244 controls). Using the VO2max  Z-score equations, aerobic fitness was significantly lower in obese/overweight CHD children than that in matched obese/overweight control children (-0.43 ± 1.27 vs. -0.01 ± 1.09; P = 0.02, respectively), and the proportion of children with impaired aerobic fitness was significantly more important in obese/overweight CHD children than in matched controls (17% vs.6%, P = 0.02, respectively). The paediatric VO2max  Z-score reference equations also identified specific complex CHD at risk of aerobic fitness impairment (univentricular heart and right outflow tract anomalies). Using Cooper's weight- and height-based linear equations, similar matched-comparisons analyses found no significant group differences. CONCLUSIONS: As opposed to the existing linear models, the new paediatric VO2max  Z-score equations can discriminate the aerobic fitness of obese/overweight children with CHD from that of obese/overweight children without any chronic disease. REGISTRATION: ClinicalTrials.gov NCT04815577.

The new paediatric VO2max  Z-score reference equations found a lower aerobic fitness in obese or overweight children with CHD than that in matched obese or overweight control children and a high proportion of children with impaired aerobic fitness in obese or overweight children with CHD and identified specific complex CHD at risk of aerobic fitness impairment. As opposed to Cooper's weight-based or height-based linear equations, the new paediatric VO2max  Z-score equations can discriminate the aerobic fitness of obese or overweight children with CHD from that of obese or overweight children without any chronic disease.

Reference values of aerobic fitness in the contemporary paediatric population.

AIMS: There has been a growing interest in the use of markers of aerobic physical fitness (VO2max assessed by cardiopulmonary exercise test (CPET)) in the follow-up of paediatric chronic diseases. The dissemination of CPET in paediatrics requires valid paediatric VO2max reference values to define the upper and lower normal limits. This study aimed to establish VO2max reference Z-score values, from a large cohort of children representative of the contemporary paediatric population, including those with extreme weights. METHODS AND RESULTS: In this cross-sectional study, 909 children aged 5 to 18 years old from the general French population (development cohort) and 232 children from the general German and US populations (validation cohort) underwent a CPET, following the guidelines on high-quality CPET assessment. Linear, quadratic, and polynomial mathematical regression equations were applied to identify the best VO2max Z-score model. Predicted and observed VO2max values using the VO2max Z-score model, and the existing linear equations were compared, in both development and validation cohorts. For both sexes, the mathematical model using natural logarithms of VO2max, height, and BMI was the best fit for the data. This Z-score model could be applied to normal and extreme weights and was more reliable than the existing linear equations, in both internal and external validity analyses (https://play.google.com/store/apps/details?id=com.d2l.zscore). CONCLUSION: This study established reference Z-score values for paediatric cycloergometer VO2max using a logarithmic function of VO2max, height, and BMI, applicable to normal and extreme weights. Providing Z-scores to assess aerobic fitness in the paediatric population should be useful in the follow-up of children with chronic diseases. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04876209.

Impaired aerobic capacity in adolescents and young adults after treatment for cancer or non-malignant haematological disease.

PURPOSE: Childhood cancer survivors are at increased risk for cardiovascular disease. Maximal oxygen uptake (VO2max) is a major determinant of cardiovascular morbidity. The aim of this study was to compare aerobic capacity, measured by cardiopulmonary exercise test (CPET), of adolescents and young adults in remission with that of healthy controls and to identify the predictors of aerobic capacity in this population. METHOD: This is a controlled cross-sectional study. RESULTS: A total of 477 subjects (77 in remission and 400 controls), aged from 6 to 25 years, were included, with a mean delay between end of treatment and CPET of 2.9 ± 2.3 years in the remission group. In this group, the mean VO2max was significantly lower than in controls (37.3 ± 7.6 vs. 43.3 ± 13.1 mL/kg/min, P < 0.01, respectively), without any clinical or echocardiographic evidence of heart failure. The VAT was significantly lower in the remission group (26.9 ± 6.0 mL/kg/min vs. 31.0 ± 9.9 mL/kg/min, P < 0.01, respectively). A lower VO2max was associated with female sex, older age, higher BMI, radiotherapy, and hematopoietic stem cell transplantation. CONCLUSION: Impaired aerobic capacity had a higher prevalence in adolescents and young adults in cancer remission. This impairment was primarily related to physical deconditioning and not to heart failure. TRIAL REGISTRY: NCT04815447. IMPACT: In childhood cancer survivors, aerobic capacity is five times more impaired than in healthy subjects. This impairment mostly reflects early onset of physical deconditioning. No evidence of heart failure was observed in this population.

Cardiopulmonary fitness in children with asthma versus healthy children.

OBJECTIVES: To evaluate, with a cardiopulmonary exercise test (CPET), the cardiopulmonary fitness of children with asthma, in comparison to healthy controls, and to identify the clinical and CPET parameters associated with the maximum oxygen uptake (VO2max) in childhood asthma. DESIGN: This cross-sectional controlled study was carried out in CPET laboratories from two tertiary care paediatric centres. The predictors of VO2max were determined using a multivariable analysis. RESULTS: A total of 446 children (144 in the asthma group and 302 healthy subjects) underwent a complete CPET. Mean VO2max was significantly lower in children with asthma than in controls (38.6±8.6 vs 43.5±7.5 mL/kg/min; absolute difference (abs. diff.) of -4.9 mL/kg/min; 95% CI of (-6.5 to -3.3) mL/kg/min; p<0.01) and represented 94%±9% and 107%±17% of predicted values, respectively (abs. diff. -13%; 95% CI (-17 to -9)%; p<0.01). The proportion of children with an impaired VO2max was four times higher in the asthma group (24% vs 6%, p<0.01). Impaired ventilatory efficiency with increased VE/VCO2 slope and low breathing reserve (BR) were more marked in the asthma group. The proportion of children with a decreased ventilatory anaerobic threshold (VAT), indicative of physical deconditioning, was three times higher in the asthma group (31% vs 11%, p<0.01). Impaired VO2max was associated with female gender, high body mass index (BMI), FEV1, low VAT and high BR. CONCLUSION: Cardiopulmonary fitness in children with asthma was moderately but significantly altered compared with healthy children. A decreased VO2max was associated with female gender, high BMI and the pulmonary function. TRIAL REGISTRATION NUMBER: NCT04650464.

Aerobic fitness change with time in children with congenital heart disease: A retrospective controlled cohort study.

BACKGROUND: To evaluate the change in aerobic fitness (VO2max), measured by cardio-pulmonary exercise test (CPET), in children with congenital heart disease (CHD), compared to matched healthy controls, and identify predictors of VO2max change with time in this specific population. METHOD: This longitudinal retrospective multicentre cohort study was carried out from 2010 to 2020. We included CHD paediatric patients from the cohort of a previous cross-sectional study, who had a second CPET at least 1 year after the first one, during their follow-up. RESULTS: We included 936 children, 296 in the CHD group and 640 controls. Mean time between baseline and final CPET was 4.4 ± 1.7 years. After matching on age and gender and adjustment for age and BMI, the mean VO2max group difference was 10.5% ± 1.0% of percent-predict VO2max at baseline and increased to 19.1% ± 1.3% at final assessment. In the CHD group, the proportion of children with impaired aerobic fitness was significantly higher at final than at baseline CPET assessment (51.4% vs 20.3%; P < 0.01). The mean annual VO2max decrease was significantly worse in the CHD group than in controls (-1.88% ± 0.19% of percent-predict VO2max/year vs. -0.44% ± 0.27% of percent-predict VO2max/year, P < 0.01, respectively). In multivariate analyse, male gender, a high initial VO2max, a high BMI, and the number of cardiac surgical procedures ≥2, were predictors of the VO2max decrease with time. CONCLUSION: The VO2max decrease with time is more pronounced in children with CHD compared to healthy matched controls. This study highlighted the importance of serial CPET assessment in children with CHD. Trial registration NCT04815577.

Cardiorespiratory fitness, muscle fitness, and physical activity in children with long QT syndrome: A prospective controlled study.

Background: In children with congenital long QT syndrome (LQTS), the risk of arrhythmic events during exercise commonly makes it difficult to balance exercise restrictions versus promotion of physical activity. Nevertheless, in children with LQTS, cardiorespiratory fitness, muscle fitness, and physical activity, have been scarcely explored. Materials and methods: In this prospective, controlled, cross-sectional study, 20 children with LQTS (12.7 ± 3.7 years old) and 20 healthy controls (11.9 ± 2.4 years old) were enrolled. All participants underwent a cardiopulmonary exercise test, a muscular architecture ultrasound assessment, (cross-sectional area on right rectus femoris and pennation angle), a handgrip muscular strength evaluation, and a standing long broad jump test. The level of physical activity was determined using with a waist-worn tri-axial accelerometer (Actigraph GT3X). Results: Peak oxygen uptake (VO2peak) and ventilatory anaerobic threshold (VAT) were lower in children with LQTS than in healthy controls (33.9 ± 6.2 mL/Kg/min vs. 40.1 ± 6.6 mL/Kg/min, P = 0.010; 23.8 ± 5.1 mL/Kg/min vs. 28.8 ± 5.5 mL/Kg/min, P = 0.007, respectively). Children with LQTS had lower standing long broad jump distance (119.5 ± 33.2 cm vs. 147.3 ± 36.1 cm, P = 0.02) and pennation angle (12.2 ± 2.4° vs. 14.3 ± 2.8°, P = 0.02). No differences in terms of moderate-to-vigorous physical activity were observed (36.9 ± 12.9 min/day vs. 41.5 ± 18.7 min/day, P = 0.66), but nearly all children were below the WHO guidelines. Conclusion: Despite similar physical activity level, cardiorespiratory fitness and muscle fitness in children with LQTS were lower than in healthy controls. The origin of this limitation seemed to be multifactorial, involving beta-blocker induced chronotropic limitation, physical and muscle deconditioning. Cardiovascular rehabilitation could be of interest in children with LQTS with significant physical limitation.

Physical activity and aerobic fitness in children with inherited cardiac diseases.

BACKGROUND: Because of sports and exercise restrictions, children with inherited cardiac disease are at risk of physical deconditioning. Guidelines on sports participation in cardiovascular disease have become less restrictive over time, but their real-life application and behavioural impact have seldom been evaluated in children. AIMS: We aimed to evaluate adherence to the 2020 European Society of Cardiology guidelines on sports and exercise in children with inherited cardiac arrhythmia and inherited cardiomyopathy; we also sought to evaluate their aerobic fitness, and the behavioural impact of inherited cardiac diseases on physical activity in children. METHODS: Children aged 6-18 years with inherited cardiomyopathy or inherited cardiac arrhythmia were eligible for this cross-sectional study. Clinical, demographic and qualitative data were analysed. RESULTS: A total of 32 children were included in the study (mean age 12.7±3.5 years). Most children (81.3%) complied with the 2020 European Society of Cardiology guidelines; they were physically active and had good overall aerobic fitness, with a mean peak oxygen uptake (VO2) value of 36.5±8.0mL/kg/min (84.0±17.2% of theoretical value). As a result of personal or parental behaviour, some children at risk of sudden cardiac death did not comply with the recommended upper limit of physical activity intensity, whereas others at low risk did not comply with the lower limit. CONCLUSION: Most children with inherited cardiac arrhythmia or inherited cardiomyopathy complied with current 2020 European Society of Cardiology guidelines on sports cardiology and exercise in cardiovascular disease.

Health-related quality of life and physical activity in children with inherited cardiac arrhythmia or inherited cardiomyopathy: the prospective multicentre controlled QUALIMYORYTHM study rationale, design and methods.

BACKGROUND: Advances in paediatric cardiology have improved the prognosis of children with inherited cardiac disorders. However, health-related quality of life (QoL) and physical activity have been scarcely analysed in children with inherited cardiac arrhythmia or inherited cardiomyopathy. Moreover, current guidelines on the eligibility of young athletes with inherited cardiac disorders for sports participation mainly rely on expert opinions and remain controversial. METHODS: The QUALIMYORYTHM trial is a multicentre observational controlled study. The main objective is to compare the QoL of children aged 6 to 17 years old with inherited cardiac arrhythmia (long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, or arrhythmogenic right ventricular dysplasia), or inherited cardiomyopathy (hypertrophic, dilated, or restrictive cardiomyopathy), to that of age and gender-matched healthy subjects. The secondary objective is to assess their QoL according to the disease's clinical and genetic characteristics, the level of physical activity and motivation for sports, the exercise capacity, and the socio-demographic data. Participants will wear a fitness tracker (ActiGraph GT3X accelerometer) for 2 weeks. A total of 214 children are required to observe a significant difference of 7 ± 15 points in the PedsQL, with a power of 90% and an alpha risk of 5%. DISCUSSION: After focusing on the survival in children with inherited cardiac disorders, current research is expanding to patient-reported outcomes and secondary prevention. The QUALIMYORYTHM trial intends to improve the level of evidence for future guidelines on sports eligibility in this population. Trial registration ClinicalTrials.gov Identifier: NCT04712136, registered on January 15th, 2021 ( https://clinicaltrials.gov/ct2/show/NCT04712136 ).

Assessment of Peak Inspiratory Flow in Young Infants with Acute Viral Bronchiolitis: Physiological Basis for Initial Flow Setting in Patients Supported with High-Flow Nasal Cannula.

OBJECTIVE: To assess the inspiratory demand in young infants with acute viral bronchiolitis to provide a physiological basis for initial flow setting for patients supported with high flow nasal cannula. STUDY DESIGN: Prospective study in 44 infants up to 6 months old with acute viral bronchiolitis, admitted to a pediatric intensive care unit from November 2017 to March 2019. Airflow measurements were performed using spirometry. The primary endpoint was the inspiratory demand as measured by peak tidal inspiratory flow (PTIF). The secondary endpoints were the relationships determined between PTIF, patient weight, and disease severity. RESULTS: Median (Q25-Q75) age and weight of the patients were 37 (20-67) days and 4.3 (3.5-5.0) kg, respectively. Mean PTIF was 7.45 (95% CI 6.51-8.39, min-max: 2.40-16.00) L/minute. PTIF indexed to weight was 1.68 (95% CI 1.51-1.85, min-max: 0.67-3.00) L/kg/minute. PTIF was <2.5 L/kg/minute in 89% (95% CI 75-96) of infants. PTIF was correlated with weight (ρ= 0 .55, P < .001) but not with markers of disease severity, including modified Woods clinical asthma score, Silverman-Andersen score, respiratory rate, fraction of inspired oxygen, and PCO2. CONCLUSIONS: High flow nasal cannula therapy is used commonly to support infants with acute viral bronchiolitis. The efficiency of the device is optimal if the flow setting matches the patient's inspiratory demand. According to our results, a flow rate of <2.5 L/kg/minute would be appropriate in most situations.

Impact of Sophrology on cardiopulmonary fitness in teenagers and young adults with a congenital heart disease: The SOPHROCARE study rationale, design and methods.

BACKGROUND: Recent advances in the field of congenital heart disease (CHD) have significantly improved the overall prognosis. Now more attention is being given to health-related quality of life (HRQoL) and promotion of physical activity. Non-invasive relaxation therapy may be effective in cardiac patients concerned with exercise-induced dyspnoea. The SOPHROCARE randomised trial aims to assess the impact of Caycedian Sophrology on cardiopulmonary fitness in adolescents and young adults with CHD. METHODS: The SOPHROCARE trial is a nationwide, multicentre, randomised, controlled study in CHD patients aged from 13 to 25 years old. Patients will be randomised into 2 groups (8 Sophrology group sessions vs. no intervention). The primary outcome is the change in percent predicted maximum oxygen uptake (VO2max) between baseline and 12-month follow-up. A total of 94 patients in each group is required to observe a significant increase of 10% in VO2max with a power of 80% and an alpha risk of 5%. The secondary outcomes are: clinical outcomes, cardiopulmonary exercise test parameters (VE/VCO2 slope, ventilatory anaerobic threshold, oxygen pulse, respiratory response to hypercapnia), health-related quality of life score (PedsQL), physical and psychological status. CONCLUSION: After focusing on the survival in CHD, current research is opening on secondary prevention and patient-related outcomes. We sought to assess in the SOPHROCARE trial, if a Sophrology program, could improve exercise capacity and quality of life in youth with CHD. TRIAL REGISTRATION: Clinicaltrials.gov (NCT03999320).