Implications of right aortic arch prenatal diagnosis: the multicentric nationwide ARCADE cohort.

OBJECTIVES: This study aims to describe the various presentations of the prenatally diagnosed isolated right aortic arch (RAA), that is, without associated congenital heart defect and to evaluate the impact of prenatal diagnosis of isolated RAA in terms of postnatal outcome. METHOD: In this multicentric retrospective study, from 2010 to 2019, all live births with a prenatal ultrasound diagnosis of isolated RAA were included, with a 1-year postnatal follow-up. The concordance between the different diagnostic steps (prenatal ultrasound, postnatal ultrasound and postnatal CT scan) was evaluated using Gwet's AC1 coefficient. RESULTS: A total of 309 cases of prenatally diagnosed RAA were analysed, most of which had a left ductus arteriosus (83%). The concordance between prenatal and postnatal ultrasound diagnosis was excellent regarding the RAA type (AC1=0.97, 95% CI=(0.94 to 0.99)). The rare discrepancies mainly involved non-diagnosed or misdiagnosed double aortic arch (2%). CT scan was performed in 108 neonates (35%) and the concordance between prenatal ultrasound and postnatal CT scan was good regarding the RAA diagnosis (AC1=0.80, 95% CI=(0.69 to 0.90)) but poor regarding the distribution of brachiocephalic vessels (AC1=0.21, 95% CI=(0.06 to 0.36)). An associated genetic anomaly was sought for in half of the cases and identified in 4% of the cohort. During the first year of life, 50 (18%) infants presented with vascular ring symptoms and 24 (8%) underwent aortic arch surgery. CONCLUSION: This multicentric nationwide cohort of 309 prenatally diagnosed isolated RAA demonstrated the reliability of prenatal screening, highlighted the rare cases of discrepancies between prenatal and postnatal diagnosis and underlined the value of CT scan to improve the postnatal follow-up. TRIAL REGISTRATION NUMBER: NCT04029064.

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.

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.

Use of speckle tracking echocardiography to detect late anthracycline-induced cardiotoxicity in childhood cancer: A prospective controlled cross-sectional study.

BACKGROUND: This study aimed to detect late sub-clinical patterns of cardiac dysfunction using speckle tracking echocardiography (STE) in children with cancer remission more than 12 months after the end of anthracycline treatment. METHODS: This prospective controlled study enrolled 196 children, 98 of which had been treated with anthracyclines (mean age 10.8 ± 3.6 years; 51% female) and 98 were age- and gender-matched healthy subjects in a 1:1 case-control design. Conventional echocardiographic variables were collected for left ventricle (LV) and right ventricle (RV). STE analyses were performed in the LV longitudinal, radial, and circumferential displacements and in the RV free wall longitudinal displacement. The association between LV global longitudinal strain (GLS) and the main clinical and biological parameters was evaluated. RESULTS: After a mean time interval of 5.1 ± 3.2 years since the end of chemotherapy (mean cumulative anthracycline dose of 192 ± 96 mg/m2), conventional echocardiographic measures were normal. GLS was significantly decreased in the anthracycline group (-19.1% vs. -21.5%, P < 0.0001), with a higher proportion of children with abnormal values (Z-score < -2 in 18.6% vs. 1.0%, P < 0.0001). No association was found between GLS and clinical or biological parameters. Circumferential strain was significantly worse in the anthracycline group (-16.8% vs. -19.4%, P < 0.0001), and radial strain significantly better (+51.4% vs. +35.9%, P < 0.0001). RV conventional echocardiography and STE parameters were normal and not different between anthracycline and control groups. CONCLUSIONS: The existence of a modified LV strain despite normal LV function in children treated with anthracyclines represents an important perspective for cardiomyopathy surveillance in childhood cancer survivors. Clinical Trial Registration -ClinicalTrials.gov Identifier: NCT02893787.

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 ).

Health-related quality of life in children with congenital heart disease aged 5 to 7 years: a multicentre controlled cross-sectional study.

BACKGROUND: In the context of tremendous progress in congenital cardiology, more attention has been given to patient-related outcomes, especially in assessing health-related quality of life (HRQoL) of patients with congenital heart diseases (CHD). However, most studies have mainly focused on teenagers or adults and currently, few HRQoL controlled data is available in young children. This study aimed to evaluate HRQoL of children with CHD aged 5 to 7 y.o., in comparison with contemporary peers recruited in school, as well as the factors associated with HRQoL in this population. METHODS: This multicentre controlled prospective cross-sectional study included 124 children with a CHD (mean age = 6.0 ± 0.8 y, 45% female) during their outpatient visit and 125 controls (mean age = 6.2 ± 0.8 y, 54% female) recruited at school. A generic paediatric HRQoL instrument was used (PedsQL 4.0). RESULTS: Self-reported HRQoL in children with CHD was similar to controls, overall (73.5 ± 1.2 vs. 72.8 ± 1.2, P = 0.7, respectively), and for each dimension. Parents-reported HRQoL was significantly lower in the CHD group than in controls. HRQoL was predicted by the disease severity and by repeated invasive cardiac procedures (surgery or catheterization). CONCLUSION: HRQoL in young children with CHD aged 5 to 7 years old was good and similar to controls. This study contributed to the growing body of knowledge on HRQoL in congenital cardiology and emphasized the need for child and family support in the most complex CHD. Trial registration This study was approved by the institutional review board of Montpellier University Hospital (2019_IRB-MTP_02-19) on 22 February 2019 and was registered on ClinicalTrials.gov (NCT03931096) on 30 April 2019, https://clinicaltrials.gov/ct2/show/NCT03931096 .

Impaired pulmonary function and its association with clinical outcomes, exercise capacity and quality of life in children with congenital heart disease.

BACKGROUND: Impaired pulmonary function is an independent predictor of mortality in adult congenital heart disease (CHD), but has been scarcely studied in the paediatric CHD population. AIMS: To compare the pulmonary function of children with CHD to healthy controls, and evaluate its association with clinical outcomes, exercise capacity, and quality of life. METHODS: Cross-sectional multicentre study among 834 children (555 CHD and 279 control subjects) who underwent a complete spirometry and a cardiopulmonary exercise test (CPET). The 5th centile (Z-score = -1.64) was used to define the lower limit of normal. The association of clinical and CPET variables with spirometry was studied using a multivariate analysis. Children and their parents filled in the Kidscreen health-related quality of life questionnaire. RESULTS: Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) Z-scores values were lower in children with CHD than controls (-0.4 ±â€¯1.5 vs. 0.4 ±â€¯1.3, P < 0.001 and -0.5 ±â€¯1.4 vs. 0.4 ±â€¯1.2, P < 0.001, respectively), without any obstructive airway disorder. Restrictive pattern was more frequent in CHD patients than in controls (20% vs. 4%, P < 0.0001). FVC Z-scores were predominantly impaired in complex CHD, such as heterotaxy (-1.1 ±â€¯0.6), single ventricle (-1.0 ±â€¯0.2), and complex anomalies of the ventricular outflow tracts (-0.9 ±â€¯0.1). In multivariate analysis, FVC was associated with age, body mass index, peak oxygen uptake, genetic anomalies, the number of cardiac surgery and cardiac catheter procedures. FVC and FEV1 correlated with self and proxy-related quality of life scores. CONCLUSION: These results suggest that pulmonary function should be monitored early in life, from childhood, in the CHD population. TRIAL REGISTRATION NUMBER: NCT01202916, post-results.

Prognosis of severe congenital heart diseases: Do we overestimate the impact of prenatal diagnosis?

BACKGROUND: Prenatal diagnosis of congenital heart disease (CHD) is controversial because of unclear benefits in terms of morbidity and mortality, and issues with healthcare costs and organization. AIM: To compare, in children with severe CHD, 1-year morbidity and mortality between prenatal and postnatal diagnosis groups. METHODS: All pregnancies and children aged<1 year with a diagnosis of severe CHD were collected over a 5-year period from our database. Severe CHDs were defined as lethal cases, cases leading to medical termination of pregnancy, or children requiring surgery and/or interventional catheterization and/or hospitalization during their first year of life. The primary endpoint was 1-year mortality rate among live births. RESULTS: Overall, 322 cases of severe CHD were identified; 200 had a prenatal diagnosis and there were 97 terminations of pregnancy. Of the 225 live births, 34 died before the age of 1 year. The 1-year mortality rate was not significantly different between prenatal and postnatal groups (16.7% vs. 13.9%; p=0.13). In the prenatal group, prostaglandin use was more important and precocious, duration of hospitalization stay was longer, extracardiac complications were less common and cardiac surgery was performed more frequently and later. An association with chromosomal or syndromic anomalies was a risk factor for 1-year mortality. CONCLUSIONS: Prenatal diagnosis of severe CHD had an impact on the decision regarding termination of pregnancy, but not on the 1-year prognosis among live births. We should now use large multicentre CHD registries to determine the impact of prenatal diagnosis on postnatal management, neurological prognosis and quality of life.

Atrial septal defect and exercise capacity: value of cardio-pulmonary exercise test in assessment and follow-up.

Nearly four decades ago, the World Health Organization stated that functional capacity explorations best reflected the impact of a chronic disease on quality of life. Today, cardio-pulmonary exercise test (CPET) is recommended in the follow-up of patients with congenital heart diseases (CHDs). Indeed, the maximum oxygen uptake (VO2max) and the ventilatory efficiency (VE/VCO2 slope) correlate with both the prognosis and the quality of life in this population. Atrial septal defects (ASDs) represent the second most frequent CHD and are usually considered as simple CHDs. However, the exercise capacity of ASD patients may be impaired. Therefore, the CPET provides important information in assessment and follow-up of patients with ASDs, for both children and adults. Exercise capacity of patients with unrepaired ASDs depends on the importance of the shunt, the right ventricular (RV) function and volume overload, the level of pulmonary arterial pressure, and the occurrence of arrhythmias. For repaired ASDs, exercise capacity also depends on the delay before closure and the type of procedure (catheter or surgery). In most cases, the exercise capacity is nearly normal and CPET contributes to promote sports participation. In addition, a regular CPET follow-up is necessary to evaluate the occurrence, severity and physiological mechanisms of comorbidities, i.e., heart failure, pulmonary hypertension and arrhythmia. Furthermore, CPET follow-up in patients with ASDs may detect early onset of muscular deconditioning, for which cardiac rehabilitation may be considered.

Cardiopulmonary fitness in children with congenital heart diseases versus healthy children.

OBJECTIVE: We aimed to compare the cardiopulmonary fitness of children with congenital heart diseases (CHD) with that of age-adjusted and gender-adjusted controls. We also intended to identify clinical characteristics associated with maximum oxygen uptake (VO2max) in this population. METHODS AND RESULTS: We included in a cross-sectional multicentre study a total of 798 children (496 CHD and 302 controls) who underwent a complete cardiopulmonary exercise test (CPET). The association of clinical characteristics with VO2max was studied using a multivariate analysis. Mean VO2max in the CHD group and control represented 93%±20% and 107%±17% of predicted values, respectively. VO2max was significantly lower in the CHD group, overall (37.8±0.3vs 42.6±0.4 mL/kg/min, P<0.0001) and for each group (P<0.05). The mean VO2max decline per year was significantly higher in CHD than in the controls overall (-0.84±0.10 vs -0.19±0.14 mL/kg/min/year, P<0.01), for boys (-0.72±0.14vs 0.11±0.19 mL/kg/min/year, P<0.01) and for girls (-1.00±0.13 vs -0.55±0.21 mL/kg/min/year, P=0.05). VO2max was associated with body mass index, ventilatory anaerobic threshold, female gender, restrictive ventilatory disorder, right ventricle systolic hypertension, tricuspid regurgitation, the number of cardiac catheter or surgery procedures, and the presence of a genetic anomaly. CONCLUSIONS: Although the magnitude of the difference was not large, VO2max among children with CHD was significantly lower than in normal children. We suggest performing CPET in routine follow-up of these patients. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01202916;Post-results.

[Cardiac rehabilitation for children and adults with congenital heart disease]. / Réadaptation cardiaque de l'enfant et l'adulte avec une cardiopathie congénitale.

Advances in heart surgery over the past 30 years have significantly improved the prognosis of congenital heart diseases (CHD). Therefore, the epidemiology of CHD has changed dramatically with a shift of mortality from pediatrics to adulthood and an increased prevalence of complex CHD. Today, caregivers and patients focus their interests to new perspectives: improving the quality of life, practicing sports, improving psychosocial care. Cardiac rehabilitation is completely integrated in these new therapeutic strategies. The starting point is the cardiopulmonary exercise test (CPET), with the measurement of oxygen uptake, or "VO2". CPET is now recommended in the follow-up of the adults with CHD. Maximum oxygen uptake correlates to the quality of life of children and adults with CHD. The principles of the rehabilitation in patients with heart failure may usually be applied to CHD patients. Some studies in complex CHD showed improvement of VO2 and quality of life after rehabilitation, without any adverse events. However few physicians have the experience in rehabilitation among CHD patients, especially children. Randomized trials on cardiac rehabilitation in adult and pediatric CHD patients are essential to increase the level of evidence and lead to specific guidelines in this population.

Parental electrocardiographic screening identifies a high degree of inheritance for congenital and childhood nonimmune isolated atrioventricular block.

BACKGROUND: The origin of congenital or childhood nonimmune isolated atrioventricular (AV) block remains unknown. We hypothesized that this conduction abnormality in the young may be a heritable disease. METHODS AND RESULTS: A multicenter retrospective study (13 French referral centers, from 1980-2009) included 141 children with AV block diagnosed in utero, at birth, or before 15 years of age without structural heart abnormalities and without maternal antibodies. Parents and matched control subjects were investigated for family history and for ECG screening. In parents, a family history of sudden death or progressive cardiac conduction defect was found in 1.4% and 11.1%, respectively. Screening ECGs from 130 parents (mean age 42.0 ± 6.8 years, 57 couples) were compared with those of 130 matched healthy control subjects. All parents were asymptomatic and in sinus rhythm, except for 1 with undetected complete AV block. Conduction abnormalities were more frequent in parents than in control subjects, found in 50.8% versus 4.6%, respectively (P<0.001). A long PR interval was found in 18.5% of the parents but never in control subjects (P<0.0001). Complete or incomplete right bundle-branch block was observed in 39.2% of the parents and 1.5% of the control subjects (P<0.0001). Complete or incomplete left bundle-branch block was found in 15.4% of the parents and 3.1% of the control subjects (P<0.0006). Estimated heritability for isolated conduction disturbances was 91% (95% confidence interval, 80%-100%). SCN5A mutation screening identified 2 mutations in 2 patients among 97 children. CONCLUSIONS: ECG screening in parents of children affected by idiopathic AV block revealed a high prevalence of conduction abnormalities. These results support the hypothesis of an inheritable trait in congenital and childhood nonimmune isolated AV block.

Hyperventilation during exercise in very low birth weight school-age children may implicate inspiratory muscle weakness.

OBJECTIVES: To study the ventilatory response during exercise in 8- to 10-year-old children born in 1998 to 2000 with a birthweight <1500 g (very low birthweight [VLBW]). STUDY DESIGN: We studied 19 VLBW children and 20 full-term children paired for age and sex. A physical activity questionnaire was administered. Lean body mass, spirometry, and maximal inspiratory pressure were assessed at rest. Gas exchange, breathing pattern, and the tension-time index of the inspiratory muscles, a noninvasive indicator of inspiratory muscle effort, were evaluated during a continuous incremental cycling protocol. RESULTS: VLBW children had lower weight, height, lean body mass, and maximal inspiratory pressure than control subjects. Their physical activity level was not different. During exercise, they had a higher respiratory rate and minute ventilation for the same metabolic level (VCO(2)/kg) and a higher tension-time index of the inspiratory muscles for the same exercise level (percentage of maximal oxygen consumption). CONCLUSIONS: The lower inspiratory muscle strength observed in school-age VLBW children resulted in a higher inspiratory effort during incremental exercise. The rapid but not shallow breathing pattern adopted by this population during exercise may have been in response to their lower inspiratory muscle resistance to fatigue. VLBW children complaining of dyspnea should be investigated with exercise testing.