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.

Cardiac magnetic resonance ventricular parameters correlate with cardiopulmonary fitness in patients with functional single ventricle.

Owing to advances in medical and surgical fields, patients with single ventricle (SV) have a greatly improved life expectancy. However, progressive functional deterioration is observed over time, with a decrease in cardiopulmonary fitness. This study aimed to identify, in patients with SV, the association between cardiac magnetic resonance imaging (CMR) parameters and change in cardiopulmonary fitness assessed by cardiopulmonary exercise test (CPET), and if certain thresholds could anticipate a decline in aerobic fitness. Patients with an SV physiology were retrospectively screened from 2011 and 2021 in a single-centre observational study. We evaluated (1) the correlation between baseline CMR and CPET parameters, (2) the association between baseline CMR results and change in peak oxygen uptake (peak VO2), and (3) the cut-off values of end-diastolic and end-systolic volume index in patients with an impaired cardiopulmonary fitness (low peak VO2 and/or high VE/VCO2 slope). 32 patients were included in the study. End-systolic volume index (r = 0.37, p = 0.03), end-diastolic volume index (r = 0.45, p = 0.01), and cardiac index (r = 0.46, p = 0.01) correlated with the VE/VCO2 slope. End-systolic ventricular volume (r = - 0.39, p = 0.01), end-diastolic ventricular volume (r = - 0.38, p = 0.01), and cardiac output (r = - 0.45, p < 0.01) inversely correlated with the peak VO2. In multivariate analysis, the cardiac index obtained from baseline CMR was inversely associated with the change in peak VO2 (p < 0.01). An end-diastolic volume index > 101 ml/m2 and an end-systolic volume index > 47 ml/m2 discriminated patients with impaired cardiopulmonary fitness. CMR parameters correlate with cardiopulmonary fitness in patients with SV and can therefore be useful for follow-up and therapeutic management of these patients.

Frailty and Cognitive Function in Middle-Aged and Older Adults With Congenital Heart Disease.

BACKGROUND: Life expectancy of patients with congenital heart disease (CHD) has increased rapidly, resulting in a growing and aging population. Recent studies have shown that older people with CHD have higher morbidity, health care use, and mortality. To maintain longevity and quality of life, understanding their evolving medical and psychosocial challenges is essential. OBJECTIVES: The authors describe the frailty and cognitive profile of middle-aged and older adults with CHD to identify predictor variables and to explore the relationship with hospital admissions and outpatient visits. METHODS: Using a cross-sectional, multicentric design, we included 814 patients aged ≥40 years from 11 countries. Frailty phenotype was determined using the Fried method. Cognitive function was assessed by the Montreal Cognitive Assessment. RESULTS: In this sample, 52.3% of patients were assessed as robust, 41.9% as prefrail, and 5.8% as frail; 38.8% had cognitive dysfunction. Multinomial regression showed that frailty was associated with older age, female sex, higher physiologic class, and comorbidities. Counterintuitively, patients with mild heart defects were more likely than those with complex lesions to be prefrail. Patients from middle-income countries displayed more prefrailty than those from higher-income countries. Logistic regression demonstrated that cognitive dysfunction was related to older age, comorbidities, and lower country-level income. CONCLUSIONS: Approximately one-half of included patients were (pre-)frail, and more than one-third experienced cognitive impairment. Frailty and cognitive dysfunction were identified in patients with mild CHD, indicating that these concerns extend beyond severe CHD. Assessing frailty and cognition routinely could offer valuable insights into this aging population.

Early hybrid cardiac rehabilitation in congenital heart disease: the QUALIREHAB trial.

BACKGROUND AND AIMS: Cardiopulmonary fitness in congenital heart disease (CHD) decreases faster than in the general population resulting in impaired health-related quality of life (HRQoL). As the standard of care seems insufficient to encourage and maintain fitness, an early hybrid cardiac rehabilitation programme could improve HRQoL in CHD. METHODS: The QUALIREHAB multicentre, randomized, controlled trial evaluated and implemented a 12-week centre- and home-based hybrid cardiac rehabilitation programme, including multidisciplinary care and physical activity sessions. Adolescent and young adult CHD patients with impaired cardiopulmonary fitness were randomly assigned to either the intervention (i.e. cardiac rehabilitation) or the standard of care. The primary outcome was the change in HRQoL from baseline to 12-month follow-up in an intention-to-treat analysis. The secondary outcomes were the change in cardiovascular parameters, cardiopulmonary fitness, and mental health. RESULTS: The expected number of 142 patients was enroled in the study (mean age 17.4 ± 3.4 years, 52% female). Patients assigned to the intervention had a significant positive change in HRQoL total score [mean difference 3.8; 95% confidence interval (CI) 0.2; 7.3; P = .038; effect size 0.34], body mass index [mean difference -0.7 kg/m2 (95% CI -1.3; -0.1); P = .022; effect size 0.41], level of physical activity [mean difference 2.5 (95% CI 0.1; 5); P = .044; effect size 0.39], and disease knowledge [mean difference 2.7 (95% CI 0.8; 4.6); P = .007; effect size 0.51]. The per-protocol analysis confirmed these results with a higher magnitude of differences. Acceptability, safety, and short-time effect of the intervention were good to excellent. CONCLUSIONS: This early hybrid cardiac rehabilitation programme improved HRQoL, body mass index, physical activity, and disease knowledge, in youth with CHD, opening up the possibility for the QUALIREHAB programme to be rolled out to the adult population of CHD and non-congenital cardiac disease.

Children With Cardiac Disease and Heat Exposure: Catastrophic Converging Consequences?

The detrimental impact of extreme heat exposure on the health and well-being of children is widely acknowledged. The direct and indirect effects of climate change have led to an increased risk of certain cardiovascular events which may be particularly harmful to children who are born with, or develop, heart disease. PURPOSE: To highlight the worrying paucity of investigative research aimed at differentiating how higher ambient temperatures further tax an already compromised cardiovascular system in children. METHODS: This commentary describes basic thermoregulatory concepts relevant to the healthy pediatric population and summarizes common heart diseases observed in this population. RESULTS: We describe how heat stress and exercise are important factors clinicians should more readily consider when treating children with heart disease. Countermeasures to physical inactivity are suggested for children, parents, clinicians, and policymakers to consider. CONCLUSIONS: As sudden, excessive heat exposures continue to impact our rapidly warming world, vulnerable populations like children with underlying heart conditions are at greater heat health risk, especially when coupled with the negative physical activity and fitness trends observed worldwide.

Ryanodine receptor dysfunction causes senescence and fibrosis in Duchenne dilated cardiomyopathy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked disorder characterized by progressive muscle weakness due to the absence of functional dystrophin. DMD patients also develop dilated cardiomyopathy (DCM). We have previously shown that DMD (mdx) mice and a canine DMD model (GRMD) exhibit abnormal intracellular calcium (Ca2+) cycling related to early-stage pathological remodelling of the ryanodine receptor intracellular calcium release channel (RyR2) on the sarcoplasmic reticulum (SR) contributing to age-dependent DCM. METHODS: Here, we used hiPSC-CMs from DMD patients selected by Speckle-tracking echocardiography and canine DMD cardiac biopsies to assess key early-stage Duchenne DCM features. RESULTS: Dystrophin deficiency was associated with RyR2 remodelling and SR Ca2+ leak (RyR2 Po of 0.03 ± 0.01 for HC vs. 0.16 ± 0.01 for DMD, P < 0.01), which led to early-stage defects including senescence. We observed higher levels of senescence markers including p15 (2.03 ± 0.75 for HC vs. 13.67 ± 5.49 for DMD, P < 0.05) and p16 (1.86 ± 0.83 for HC vs. 10.71 ± 3.00 for DMD, P < 0.01) in DMD hiPSC-CMs and in the canine DMD model. The fibrosis was increased in DMD hiPSC-CMs. We observed cardiac hypocontractility in DMD hiPSC-CMs. Stabilizing RyR2 pharmacologically by S107 prevented most of these pathological features, including the rescue of the contraction amplitude (1.65 ± 0.06 µm for DMD vs. 2.26 ± 0.08 µm for DMD + S107, P < 0.01). These data were confirmed by proteomic analyses, in particular ECM remodelling and fibrosis. CONCLUSIONS: We identified key cellular damages that are established earlier than cardiac clinical pathology in DMD patients, with major perturbation of the cardiac ECC. Our results demonstrated that cardiac fibrosis and premature senescence are induced by RyR2 mediated SR Ca2+ leak in DMD cardiomyocytes. We revealed that RyR2 is an early biomarker of DMD-associated cardiac damages in DMD patients. The progressive and later DCM onset could be linked with the RyR2-mediated increased fibrosis and premature senescence, eventually causing cell death and further cardiac fibrosis in a vicious cycle leading to further hypocontractility as a major feature of DCM. The present study provides a novel understanding of the pathophysiological mechanisms of the DMD-induced DCM. By targeting RyR2 channels, it provides a potential pharmacological treatment.

Generation of patient-specific induced pluripotent stem cell lines with Type 2 Long QT Syndrome and the KCNH2 c.379C > T pathogenic variant.

Type 2 Long QT Syndrome (LQT2) is a rare genetic heart rhythm disorder causing life-threatening arrhythmias. We derived induced pluripotent stem cell (iPSC) lines from two patients with LQT2, aged 18 and 6, both carrying a heterozygous missense mutation on the 3rd and 11th exons of KCNH2. The iPSC lines exhibited normal genomes, expressed pluripotent markers, and differentiated into trilineage embryonic layers. These patient-specific iPSC lines provide a valuable model to study the molecular and functional impact of the hERG channel gene mutation in LQT2 and to develop personalized therapeutic approaches for this syndrome.

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 .

Think out of the box: association of left congenital diaphragmatic hernia and abnormal origin of the right pulmonary artery : A train can hide another.

BACKGROUND: We report the occurrence of a severe pulmonary hypertension (PH) in a neonate affected by a left congenital diaphragmatic hernia (CDH). PH in this patient was associated with an abnormal origin of the right pulmonary artery from the right brachiocephalic artery. This malformation, sometimes named hemitruncus arteriosus, has to the best of our knowledge never been reported in association with a CDH. CASE PRESENTATION: A male newborn was hospitalized from birth in the neonatal intensive care unit after prenatal diagnosis of a left CDH. Ultrasound examination at 34 weeks of gestational age evaluated the observed-to-expected lung-to-head ratio at 49%. Birth occurred at 38+ 5 weeks of gestational age. Soon after admission, severe hypoxemia, i.e., preductal pulse oximetry oxygen saturation (SpO2) < 80%, prompted therapeutic escalation including the use of high frequency oscillatory ventilation with fraction of inspired oxygen (FiO2) 100% and inhaled nitric oxide (iNO). Echocardiography assessment revealed signs of severe PH and normal right ventricle function. Despite administration of epoprostenolol, milrinone, norepinephrine, and fluid loadings with albumin and 0.9% saline, hypoxemia remained severe, preductal SpO2 inconsistently greater than or equal to 80-85% and post ductal SpO2 lower on average by 15 points. This clinical status remained unchanged during the first 7 days of life. The infant's clinical instability was incompatible with surgical intervention, while chest X-ray showed a relatively preserved lung volume, especially on the right side. This prompted an additional echocardiography, aimed at searching an explanation of this unusual evolution and found an abnormal origin of the right pulmonary artery, which was confirmed on computed tomography angiography subsequently. A change in the medical strategy was decided, with the suspension of pulmonary vasodilator treatments, the administration of diuretics, and the decrease in norepinephrine dose to decrease the systemic-to-pulmonary shunt. Progressive improvement in the infant respiratory and hemodynamic status enabled to perform CDH surgical repair 2 weeks after birth. CONCLUSIONS: This case recalls the interest of systematic analysis of all potential causes of PH in a neonate with CDH, a condition frequently associated with various congenital malformations.

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.

Health-Related Quality of Life and Its Association With Outcomes in Adults With Congenital Heart Disease and Heart Failure: Insight From FRESH-ACHD Registry.

Background Quality of Life (QoL) is a prognostic factor in heart failure (HF) of patients with acquired cardiac disease. The aim of this study was to determine the predictive value of QoL on outcomes in adults with congenital heart disease (ACHD) and HF. Methods and Results Quality of life of 196 adults with congenital heart disease with clinical heart failure (HF) (mean age: 44.3±13.8 years; 51% male; 56% with complex congenital heart disease; 47% New York Heart Association class III/IV) included in the prospective multicentric registry FRESH-ACHD (French Survey on Heart Failure-Adult with Congenital Heart Disease) was assessed using the 36-Item Short Form Survey (SF-36), a patient-reported survey. The primary end point was defined by all-cause death, HF-related hospitalization, heart transplantation, and mechanical circulatory support. At 12 months, 28 (14%) patients reached the combined end point. Patients with low quality of life experienced major adverse events more frequently (logrank P=0.013). On univariate analysis, lower score at physical functioning (hazard ratio [HR], 0.98 [95% CI, 0.97-0.99]; P=0.008), role limitations related to physical health (HR, 0.98 [95% CI, 0.97-0.99]; P=0.008), and general health dimensions of the SF-36 (HR, 0.97 [95% CI, 0.95-0.99]; P=0.002) were significantly predictive of cardiovascular events. However, after multivariable analysis, SF-36 dimensions were no longer significantly associated with the primary end point. Conclusions Patients with congenital heart disease with HF and poor quality of life experience severe events more frequently, making quality of life assessment and rehabilitation programs essential to alter their trajectory.

Correlation between three-dimensional echocardiography and cardiopulmonary fitness in patients with univentricular heart: A cross-sectional multicentre prospective study.

BACKGROUND: The prognosis of patients with a functional single ventricle has improved, with better cardiopulmonary fitness, health-related quality of life and survival. Conventional echocardiography remains the first-line technique in single ventricle follow-up. Three-dimensional (3D) echocardiography has shown recent value in congenital cardiology, but its ability to predict functional status in patients with a single ventricle remains unknown. AIM: To evaluate, in patients with a single ventricle, the association between 3D echocardiography variables and functional status determined by cardiopulmonary fitness. METHODS: Children and adults with a functional single ventricle were prospectively enrolled in this multicentre study. Cardiopulmonary fitness was assessed by cardiopulmonary exercise test, with measures of maximum oxygen uptake (VO2max) and ventilatory efficiency (VE/VCO2 slope). 3D echocardiography was performed with off-line reproducibility analyses, using TomTec Arena™ software. Health-related quality of life was assessed using the SF-36 questionnaire. RESULTS: A total of 33 patients were screened, and 3D echocardiography analyses were feasible in 22 subjects (mean age 28±9years). 3D echocardiography ejection fraction correlated with percent-predicted VO2max (r=0.64, P<0.01), VE/VCO2 slope (r=-0.41, P=0.05), two-dimensional echocardiography ejection fraction (r=0.55, P<0.01) and health-related quality of life physical functioning dimension (r=0.56, P=0.04). 3D echocardiography indexed end-systolic volume correlated with percent-predicted VO2max (r=-0.45, P=0.03) and VE/VCO2 slope (r=0.65, P<0.01). 3D echocardiography reproducibility was good. CONCLUSIONS: Single ventricle ejection fraction and volumes measured by 3D echocardiography correlated with cardiopulmonary fitness, as determined by two main prognostic cardiopulmonary exercise test variables: VO2max and VE/VCO2 slope. Despite good reproducibility, 3D echocardiography feasibility remained limited. 3D echocardiography may be of value in single ventricle follow-up, provided that the technique and analysis software are improved.

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.

Risk factors for early occurrence of malnutrition in infants with severe congenital heart disease.

To identify the risk factors of early occurrence of malnutrition in infants with severe congenital heart disease (CHD) during their first year of life. Retrospective longitudinal multicenter study carried out from January 2014 to December 2020 in two tertiary care CHD centers. Four CHD hemodynamic groups were identified. Malnutrition was defined by a Waterlow score under 80% and/or underweight under -2 standard deviations. A total of 216 infants with a severe CHD, e.g., requiring cardiac surgery, cardiac catheterization, or hospitalization for heart failure during their first year of life, were included in the study. Malnutrition was observed among 43% of the cohort, with the highest prevalence in infants with increased pulmonary blood flow (71%) compared to the other hemodynamic groups (p < 0.001). In multivariate analysis, low birthweight (OR 0.62, 95% CI 0.44-0.89, p = 0.009), CHD with increased pulmonary blood flow (OR 4.80, 95% CI 1.42-16.20, p = 0.08), heart failure (OR 9.26, 95% CI 4.04-21.25, p < 0.001), and the number of hospitalizations (OR 1.35, 95% CI 1.08 l-1.69, p = 0.009) during the first year of life were associated with malnutrition (AUC 0.85, 95% CI 0.79-0.90).  Conclusions: In infants with a severe CHD, early occurrence of malnutrition during the first year of life affected a high proportion of subjects. CHD with increased pulmonary blood flow, low birthweight, heart failure, and repeated hospitalizations were risk factors for malnutrition. Further studies are required to identify optimal nutritional support in this population. What is Known: • Malnutrition is a known morbidity and mortality factor in children with severe congenital heart disease. What is New: • Early occurrence of malnutrition during the first year of life in infant severe congenital heart disease (CHD) was high (43%). • CHD with increased pulmonary blood flow, low birthweight, heart failure, and repeated hospitalizations during the first year of life were risk factors for malnutrition.

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.

Which risk score best predicts cardiovascular outcome in pregnant women with congenital heart disease?

BACKGROUND: Management of pregnancy and risk stratification in women with congenital heart diseases (CHD) are challenging, especially due to physiological haemodynamic modifications that inevitably occur during pregnancy. AIMS: To compare the accuracy of the existing pregnancy cardiovascular risk scores in prediction of maternal complications during pregnancy in CHD patients. METHOD AND RESULTS: From 2007 to 2018, all pregnant women with a CHD who delivered birth after 20 weeks of gestation were identified. The discriminating power and the accuracy of the five existing pregnancy cardiovascular risk scores [CARPREG, CARPREG II, HARRIS, ZAHARA risk scores, and modified WHO (mWHO)] were evaluated.Out of 104 pregnancies in 65 CHD patients, 29% experienced cardiovascular complications during pregnancy or post-partum. For the five scores, the observed rate of cardiovascular events was higher than the expected risk. The values of area under the ROC curve were 0.75 (0.62-0.88) for mWHO, 0.65 (0.53-0.77) for CARPREG II, 0.60 (0.40-0.80) for HARRIS, 0.59 (0.47-0.72) for ZAHARA, and 0.58 (0.43-0.73) for CARPREG. CONCLUSION: The modified WHO classification appeared to better predict cardiovascular outcome in pregnant women with CHD than the four other existing risk scores.Clinical Trial Registration: Clinicaltrials.gov: NCT04221048.

Participation in physical activity of adolescents with congenital heart disease.

BACKGROUND: Participation in physical activity improves health in individuals with congenital heart disease. However, most do not sufficiently engage in physical activity. The aim of this study was to collect information regarding the experiences of adolescents with congenital heart disease who practiced physical activities. METHODS: French adolescents aged 13-18 years, diagnosed with congenital heart disease, class I or II dyspnoea on the NYHA scale and authorized physical activity were interviewed individually about their physical activity experiences using a semi-structured format. The qualitative interview transcript data were analysed using a phenomenological approach; data analysis was performed independently by three researchers and merged at each step until saturation. RESULTS: Eleven adolescents with congenital heart disease participated. Three main themes emerged: 'own representation', 'physical activity (PA) set-up' and 'environment'. Adolescents had a generally positive view of physical activity, which was associated with positive experiences. However, they reported that their physical condition limited PA, and they wished for adapted activities. The results revealed the importance of environmental factors, for example, within the social and school environments. The participants indicated that they appreciated the social interactions that PA afforded, but that integration into a group could be difficult, especially in school, with some participants describing feelings such as anxiety, frustration or guilt when they could not participate fully. PA facilitators included familial support. However, participants noted a lack of clear medical guidance to help them choose suitable activities based on their circumstances and personal preferences. They wished for the public to be better informed about congenital heart disease to reduce stigmatism. CONCLUSIONS: This study provides valuable information for clinicians, physical educators and policy makers to help them promote physical activity and support adolescents and their families in understanding their own condition, maximizing their potential and in their choice of activities.

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.

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.

Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: An International Study.

BACKGROUND: Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown cause. We aimed to better understand familial recurrence patterns. METHODS: An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, entailing investigation of 1043 unrelated ccTGA probands. RESULTS: Laterality defects and atrioventricular block at diagnosis were observed in 29.9% and 9.3%, respectively. ccTGA was associated with primary ciliary dyskinesia in 11 patients. Parental consanguinity was noted in 3.4% cases. A congenital heart defect was diagnosed in 81 relatives from 69 families, 58% of them being first-degree relatives, including 28 siblings. The most prevalent defects in relatives were dextro-transposition of the great arteries (28.4%), laterality defects (13.6%), and ccTGA (11.1%); 36 new familial clusters were described, including 8 pedigrees with concordant familial aggregation of ccTGA, 19 pedigrees with familial co-segregation of ccTGA and dextro-transposition of the great arteries, and 9 familial co-segregation of ccTGA and laterality defects. In one family co-segregation of ccTGA, dextro-transposition of the great arteries and heterotaxy syndrome in 3 distinct relatives was found. In another family, twins both displayed ccTGA and primary ciliary dyskinesia. CONCLUSIONS: ccTGA is not always a sporadic congenital heart defect. Familial clusters as well as evidence of an association between ccTGA, dextro-transposition of the great arteries, laterality defects and in some cases primary ciliary dyskinesia, strongly suggest a common pathogenetic pathway involving laterality genes in the pathophysiology of ccTGA.