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Three-dimensional (3-D) printed models are increasingly used to enhance understanding of complex anatomy in congenital heart disease. To assess feasibility and accuracy of 3-D printed models obtained from cardiac CT scans in young children with complex congenital heart diseases. We included children with conotruncal heart anomalies who were younger than 2 years and had a cardiac CT scan in the course of their follow-up. We used cardiac CT scan datasets to generate 3-D models. To assess the models’ accuracy, we compared four diameters for each child between the CT images and the printed models, including the largest diameters (Dmax) of ventricular septal defects and aortic annulus and their minimal diameters (Dmin). We obtained images from 14 children with a mean age of 5.5 months (range 1–24 months) and a mean weight of 6.7 kg (range 3.4–14.5 kg). We generated 3-D models for all children. Mean measurement difference between CT images and 3-D models was 0.13 mm for Dmin and 0.12 mm for Dmax for ventricular septal defect diameters, and it was 0.16 mm for Dmin and −0.13 mm for Dmax for aortic annulus diameter, indicating a non-clinically significant difference. Three-dimensional printed models could be feasibly generated from cardiac CT scans in a small pediatric population with complex congenital heart diseases. This technique is highly accurate and reliably reflects the same structural dimensions when compared to CT source images.

Marfan syndrome (MFS) is a heritable connective tissue disorder (HCTD) caused by pathogenic variants in FBN1 that frequently occur de novo. Although individuals with somatogonadal mosaicisms have been reported with respect to MFS and other HCTD, the overall frequency of parental mosaicism in this pathology is unknown. In an attempt to estimate this frequency, we reviewed all the 333 patients with a disease-causing variant in FBN1. We then used direct sequencing, combined with High Resolution Melting Analysis, to detect mosaicism in their parents, complemented by NGS when a mosaicism was objectivized. We found that (1) the number of apparently de novo events is much higher than the classically admitted number (around 50% of patients and not 25% as expected for FBN1) and (2) around 5% of the FBN1 disease-causing variants were not actually de novo as anticipated, but inherited in a context of somatogonadal mosaicisms revealed in parents from three families. High Resolution Melting Analysis and NGS were more efficient at detecting and evaluating the level of mosaicism compared to direct Sanger sequencing. We also investigated individuals with a causal variant in another gene identified through our “aortic diseases genes” NGS panel and report, for the first time, on an individual with a somatogonadal mosaicism in COL5A1. Our study shows that parental mosaicism is not that rare in Marfan syndrome and should be investigated with appropriate methods given its implications in patient’s management.

Little is known about the incidence of cardiovascular events (CVEs) and their associated risk markers in children with Marfan syndrome (MFS).To assess the incidence of CVEs and determine risk markers in a cohort diagnosed with Marfan syndrome during childhood and followed for several years.From a French multicentre nationwide database, 462 patients with MFS diagnosed during childhood were included prospectively. Patients' files were screened for a period of 20 years (1993-2013). CVEs (e.g. death, aortic dissection, cardiac valve or aortic root surgery) were assessed during the prospective follow-up.Median (interquartile range) age at the end of follow-up was 17.2 (11.1-21.3) years. CVEs were reported for 35 participants (7.6%; 95% confidence interval [CI] 5.3-10.4%). First CVEs were prophylactic aortic root surgery (n=29), aortic dissection (n=4; two aged18 years) and death (n=2). Kaplan-Meier cumulative incidence of CVEs was 5.3% (95% CI 3.3-8.7%) during childhood (aged≤18 years) and 19.4% (95% CI 13.3-27.9%) at 25years of age. The cumulative rate of CVEs was higher in case of Valsalva sinus Z-score increase of≥0.1 per year (P=0.0003), maximal Valsalva sinus diameter growth speed ≥5mm per year (P=0.03), aortic regurgitation≥2 (P=0.0005) and maximal Valsalva sinus Z-score≥3 before 16 years of age (P0.0001). In a multivariable Cox proportional analysis, the Valsalva sinus Z-score remained significantly related to outcome. Considering aortic root evolution, aortic regurgitation, age at diagnosis and beta-blocker therapy were related to Valsalva sinus Z-score evolution during follow-up.CVEs in children with MFS are mainly related to prophylactic aortic root surgery. Aortic dissections are rarely observed in children. The Valsalva sinus Z-score is a strong indicator of subsequent CVEs in children with MFS. Attention to follow-up and beta-blocker observance may be warranted in high-risk children.

Background Pathogenic variants in MYH11 are associated with either heritable thoracic aortic aneurysm and dissection (HTAAD), patent ductus arteriosus (PDA) syndrome, or megacystis‐microcolon‐intestinal hypoperistalsis syndrome (MMIHS). Methods and Results We report a family referred for molecular diagnosis with HTAAD/PDA phenotype in which we found a variant at a non‐conserved position of the 5’ donor splice site of intron 32 of MYH11 potentially altering splicing (NM_002474.3:c.4578+3A>C). Although its cosegregation with disease was observed, it remained of unknown significance. Later, aortic surgery in the proband gave us the opportunity to perform a transcript analysis. This showed a skipping of the exon 32, an RNA defect previously reported to be translated to an in‐frame loss of 71 amino acids and a dominant‐negative effect in the smooth muscle myosin rod. This RNA defect is also reported in 3 other HTAAD/PDA pedigrees. Conclusion This report confirms that among rare variants in MYH11, skipping of exon 32 is recurrent. This finding is of particular interest to establish complex genotype–phenotype correlations where some alleles are associated with autosomal dominant HTAAD/PDA, while others result in recessive or dominant visceral myopathies., We report on a family with heritable thoracic aortic aneurysm and/or dissection with patent ductus arteriosus (FTAAD/PDA) caused by a variant leading to a skipping of the exon 32 in the MYH11 gene. This transcripts defect previously shown to lead to a strong dominant negative effect in the smooth muscle myosin rod is recurrent. It highlights some unclear genotype‐phenotype correlations suggested by literature with some alleles associated with autosomal dominant FTAAD/PDA while others result in recessive visceral myopathies.

Catheter ablation (CA) in children using fluoroscopy carries risks inherent to ionizing radiation exposure.The objective of this study was to demonstrate the feasibility of using low frames rate during ablation in children to maximally decrease radiation dose.Hundred sixty eight successive patients18 years of age undergoing CA performed under a 3.75 frames/second rate were retrospectively included. Demographics, procedural and dosimetry data were analysed. The effective dose (ED) was evaluated in a subgroup of 14 patients.Median age and weight were 15 years and 54kg, 72% had WPW, 10% AV node reentrant tachycardia, 10% ventricular tachycardia (atrial tachycardia, flutter and atrial fibrillation for the other cases). Acute success was achieved in 98.5% without any complication. Median procedure and fluoroscopy duration were 120 and 16minutes. Median Dose Area Product (DAP) and Air Kerma were 2.46Gy.cmLow frame rate fluoroscopy is a highly effective and safe approach in decreasing radiation exposure during CA in children without altering the success rate of the procedure. ED is low, similar to natural/leisure irradiation. This approach can be considered a good alternative to 3D-based procedures in terms of efficiency and radiation issues, at least for WPW ablations.

BackgroundAdvances 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.MethodsThe 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%.DiscussionAfter 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 registrationClinicalTrials.gov Identifier: NCT04712136, registered on January 15th, 2021 (https://clinicaltrials.gov/ct2/show/NCT04712136).

International audience; Purpose : Heritable thoracic aortic aneurysms and dissections (hTAAD) are life-threatening complications of well-known syndromic diseases or underdiagnosed nonsyndromic heritable forms (nshTAAD). Both have an autosomal dominant transmission and are genetically heterogeneous. Our objective was to describe the relevance of molecular diagnosis in these patients and the contribution of each gene in nshTAAD. Methods : Two hundred twenty-six consecutive nshTAAD probands, either young (

The aim is to conduct a pilot study to prospectively describe echocardiographic parameters in neonates with pulmonary hypertension (PH) managed according to current recommendations and to identify those parameters that could predict worsening of short-term outcomes. All neonates less than 28 days old with a diagnosis of PH were prospectively enrolled in a tertiary care center for 1 year. Two echocardiograms were performed by a trained neonatologist. The first echocardiogram was performed at the time of diagnosis, whereas the second was performed just after basic therapeutic optimization. The cohort included 27 neonates. Mean gestational age at birth was 36.1 weeks gestational age (WGA) (SD: 4) and mean birth weight was 2658 g (SD: 907). Six neonates (22%) died before day 28, with a median age at death of 48 h (IQR [33; 89]). Although the first echocardiogram showed no difference, the second highlighted a strong link between the persistence of right-to left-shunt and death (p = 0.002). We showed a link between right-to-left shunt and a poor outcome (death or morbidity) after therapeutic optimization among premature and full-term neonates suffering from PH. We recommend repeating echocardiography after basic therapeutic optimization and for prognostic purposes, taking into account only the second examination. Larger cohorts are needed to confirm these results. Supplementary Information The online version contains supplementary material available at 10.1007/s00246-021-02677-z.

Background COVID-19 triggered an unprecedented crisis affecting our society at every level. Clinical research in paediatric and congenital cardiology is currently in full development and may have been disrupted. Aims To determine the impact of COVID-19 in paediatric and congenital cardiology clinical research and to analyse decision-making and adaptation processes, from a panel of on-going academic and industry-sponsored research at the time of the pandemic. Methods This observational study was carried out in April 2020, from a CHD clinical research network involving five tertiary care paediatric and congenital cardiology centres. Investigators and clinical research assistants from each participating research centre filled in an online survey questionnaire, and each principal investigator underwent a one-hour web-based videoconference interview. Results From a total of 34 study questionnaires and 288 enrolled patients at the time of the pandemic, 18 studies were declared as totally suspended. Upon investigator's decision, after discussion on ethical issues and with facilitating support from health authorities, 16 studies were resumed. The rate of study suspension in interventional research (53%) was similar to non-interventional research (56%). Logistical problems were predominantly reported in both continued and suspended trials. Research protocols were adapted, largely thanks to telemedicine, which in some cases even improved the course of the study. Conclusions The impact of the COVID-19 pandemic on clinical research in paediatric and congenital cardiology has been limited by a rapid adaptation of all research structures and an extensive use of telemedicine at all stages of the studies.

Background: Recent advances in the field of congenital heart disease (CHD) led to an improved prognosis of the patients and in consequence the growth of a new population: the grown up with congenital heart disease. Until recently, more than 50% of these patients were lost to follow up because of the lack of specialized structures. The critical moment is the transition between paediatric and adult unit. Therapeutic education is crucial to solve this issue by helping patient to become independent and responsible. The TRANSITION randomized trial aims to assess the impact of a transition education program on the quality of life (QoL) of adolescents and young adults with CHD. Methods: multicentre, randomised, controlled, parallel arm study in CHD patients aged from 13 to 25 years old. Patients will be randomised into 2 groups (Education program vs. no intervention). The primary outcome is the change in self-reported QoL between baseline and 12-month follow-up. A total of 100 patients in each group is required to observe a significant increase of the overall QoL score of 7±13.5 points (on 100) with a power of 80% and an alpha risk of 5%. The secondary outcomes are: clinical outcomes, cardiopulmonary exercise test parameters (VO2max,VE/VCO2 slope), level of knowledge, physical and psychological status.Discussion: As the current research is opening on patient related outcomes, and as the level of proof in therapeutic education still low, we sought to assess the efficacy of a therapeutic education program on the QoL of CHD patients with a randomized trial.Trial registration: This study was approved by the National Ethics Committee (South-Mediterranean IV 2016-A01681-50) and was registered on Clinicaltrials.gov (NCT03005626) on 29th December 2016

BackgroundRecent advances in the field of congenital heart disease (CHD) led to an improved prognosis of the patients and in consequence the growth of a new population: the grown up with congenital heart disease. Until recently, more than 50% of these patients were lost to follow up because of the lack of specialized structures. The critical moment is the transition between paediatric and adult unit. Therapeutic education is crucial to solve this issue by helping patients to become independent and responsible. The TRANSITION-CHD randomized trial aims to assess the impact of a transition education program on health-related quality of life (HRQoL) of adolescents and young adults with CHD.MethodsMulticentre, randomised, controlled, parallel arm study in CHD patients aged from 13 to 25 years old. Patients will be randomised into 2 groups (education program vs. no intervention). The primary outcome is the change in self-reported HRQoL between baseline and 12-month follow-up. A total of 100 patients in each group is required to observe a significant increase of the overall HRQoL score of 7 ± 13.5 points (on 100) with a power of 80% and an alpha risk of 5%. The secondary outcomes are: clinical outcomes, cardiopulmonary exercise test parameters (peak VO2, VAT, VE/VCO2 slope), level of knowledge of the disease using the Leuven knowledge questionnaire for CHD, physical and psychological status.DiscussionAs the current research is opening on patient related outcomes, and as the level of proof in therapeutic education is still low, we sought to assess the efficacy of a therapeutic education program on HRQoL of CHD patients with a randomized trial.Trial registrationThis study was approved by the National Ethics Committee (South-Mediterranean IV 2016-A01681-50) and was registered on Clinicaltrials.gov (NCT03005626).

Introduction Sickle cell disease (SCD) is characterized by chronic hemolytic anemia and intermittent vaso-occlusive events associated with cardiac abnormalities. Aim To assess 3 dimensional (3D) echocardiographic of right ventricle (RV) volumes and function in a pediatric SCD population. Methods Eighteen patients with SCD aged 4 to 17 years old (mean age: 8.0±4 years, 56% male, body surface area (BSA) 1.0±0.35) and 18 healthy controls matched for age, gender and BSA were prospectively included and compared. Echocardiograms were performed using a commercially available ultrasound Philipps EPIQ 9 system using matrix X5–1 transducer. 3D indexed RV volumes and ejection fraction (3D- RVEF) were obtained using full volume acquisitions. RV free wall strain, tricuspid S-wave, tricuspid annular plane systolic excursion (TAPSE), indexed cardiac output, systolic pulmonary pressure (sPAP) and hemoglobin were assessed. Data were analyzed with TomtecArena© software (v2.3, Germany). Results Cardiac output was significantly higher in SCD children (4.5 vs 3.6 l/min/m2, p=0.025), as sPAP (24.9 vs 21.9 mmHg, p=0.015), 3D-RV diastolic volume (58.1 vs 47.5 ml/m2, p=0.025) and 3D-RV systolic volume (28.8 vs 21.4 ml/m2, p=0.005). 3D-RVEF and RV free wall strain were significantly lower in SCD compared to control population (respectively 51.9 vs 56.3%, p=0.018; −28.6 vs −32, p=0.017). There were no difference regarding TAPSE and doppler S-wave. Mean hemoglobin in SCD population was 9.6±1.7 g/dl. Conclusions Despite normal RV systolic function parameters, 3D-RVEF and RV free wall strain are lower in children with SCD. Chronic anemia generating volume overload and vaso-occlusive events could explain these findings. 3D sickle cell Funding Acknowledgement Type of funding source: None

Highlights • Exercise capacity in patients with CHD is lower than in the general population. • Non-invasive relaxation therapy may be effective in patients with dyspnoea. • Evidence based-medicine on relaxation therapy in the CHD population is poor. • This trial will assess the impact of Sophrology on exercise capacity in CHD patients., 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).

Cardiac arrhythmia with sudden death is rare in children but mainly due to ventricular tachycardia. In case of pulseless ventricular tachycardia, prehospital treatment is crucial with immediate cardiopulmonary resuscitation and external electrical cardioversion. We report the case of pulseless ventricular tachycardia in a child with no past medical history. Sinus rhythm was obtained after 12 min of cardiorespiratory resuscitation and three external electrical shocks. An exhaustive diagnostic approach allow us to find its origin. The clinical progression was marked by a severe encephalopathy. The authors discuss different etiologies and treatment of arrhythmia in children, reviewing the pediatric algorithm for shockable rhythm.

Background Wolff Parkinson White syndrome is responsible of junctional tachycardia and potentially sudden death in children. Precise location of accessory pathway (AP) is crucial to increase safety and success rate of ablation procedures. Known ECG localization algorithms have limited accuracy in children close to 50%. Objective The aim of study was to evaluate a new ECG algorithm relying on maximal pre-excitation (EMP) in children. Methods ECG with EMP (ventricular activation secondary to AP without His bundle activation), induced by atrial pacing or adenosine test/vagal maneuver, was prospectively recorded during an electrophysiological study in 90 consecutive children under 16, in 3 tertiary centers between 2008 and 2020. 3 blinded investigators (1: expert rythmologist, 2: pediatric cardiologist and 3: pediatric cardiologist in training) tested a new algorithm based on EMP to predict AP location and 2 validated control algorithms, from Arruda and Min Baek, relying on basal pre-excitation. Predicted locations were matched with ablation-verified AP location. Sensibility, specificity, negative/positive predictive values and reproducibility, defined as level of agreement between investigators in determining AP location, were evaluated. Results AP were Left sided in 38%, septal in 47% and right sided in 16%. With the new algorithm, predictive accuracy for the 9 exact locations was 91%, 89% and 90% for investigator 1, 2 and 3, respectively. Sensibility was 80-100% for right sided, 95–100% for left sided and 62-100% for septal AP. Concordance between investigators was excellent (k ≥ 0,86). The accuracy for the reference algorithms remain poor (45% for Arruda and 51% for Min Baek) with less concordance between investigators. Conclusion Our new algorithm based on EMP allows accurate and easy to use localization of AP in children. This algorithm can be employed before cardiac catheterization and can allow better evaluation of the benefit/risk ratio of the intervention.

Introduction 3D printed models are increasingly used to enhance understanding of complex anatomy in congenital heart disease. We aimed to assess feasibility and accuracy of 3D printed models obtained from cardiac CT scan in small pediatric population with complex congenital heart diseases. Method Patients with conotruncal heart anomalies aged less than 2 years old who had a cardiac CT scan in course of their follow-up were included. Cardiac CT scan datasets were used to generate 3D models. To assess model's accuracy, 4 diameters were compared for each patient between the CT images and the printed models, including the largest diameters (Dmax) of ventricular septal defects (VSD) and aortic annulus (AA) and their minimal diameters (Dmin). Results Images of 14 patients were obtained. Mean age was 5.5 months (1–24 months), mean weight was 6.7 kg (3.4–14.5 kg). 3D models were successfully obtained in all patients. Correlations between measurements obtained from printed models and CT images were excellent (r = 0.90 to 0.98). Mean measurement difference between CT image and 3D model was 0.13 mm for Dmin and 0.12 mm for Dmax for VSD diameters, and was 0.16 mm for Dmin and −0.13 mm for Dmax for AA diameter indicating a non-clinically significant difference ( Fig. 1 ). Conclusion 3D printed models are feasible from cardiac CT scan in small pediatric population with complex congenital heart diseases. This technic is highly accurate and reliably reflects the same structure dimensions when compared to CT source images.

Background Prevalence of early repolarisation ECG pattern (ER) has been repetitively determined in adults, but has not been reported in large unselected children populations so far. Methods ECG from 1000 successive healthy children from birth to 17years old were prospectively recorded and analyzed. ER was defined by ≥0.1mV J point elevation in at least two contiguous inferior or lateral ECG leads. Correlations with age, gender, ethnic origin, physical activity, Sokolow index and heart rate were performed. Results Prevalence of ER pattern was 23,6% (95% CI 21–26.2%) and increased after 8years of age. ER was independently correlated to a non Caucasian origin and a higher Sokolow index, but not to gender or level of physical activity. ER was independently correlated to an older age in children with heart rate Conclusion ER is present in a quarter of children of various age and is related to ethnic origin, an older age, a slower heart rate and a higher Sokolow index.

The fulminant viral myocarditis is associated to a high risk of mortality and heart transplantation in children. Anti-inflammatories and intravenous gamma globulin are used in the majority of studies but the outcome is not always favorable. In this case, we suggest an important role for antiviral therapy in children's fulminant myocarditis.

Objective Transition education programs dedicated to adolescents and young adults with congenital heart disease (CHD) aim to facilitate transfer to adult cardiology and bring more autonomy to teenagers. This prospective controlled multicentre study analysed the factors influencing the participation in a transition education program. Methods CHD patients aged 13–25 y were offered to participate in the transition program. A multiple linear regression identified the explanatory factors for participation in the program. Results A total of 123 patients (mean age 19.6 ± 3.4 y) were included in the study, with 57 participants and 66 non-participants. Both groups showed similar socio-demographic and quality of life characteristics, low level of physical activity with muscular deconditioning and high exposure to risk behaviours (71% patients with ≥1 risk factor). Patients with complex CHD (OR = 4.1, P = 0.03), poor disease knowledge (OR = 0.3, P = 0.02), risk behaviours (body piercing, OR = 5.53, P = 0.01; alcohol, OR = 3.12, P = 0.06), and aged Conclusion Many risk factors influencing the participation of adolescents and young adults with CHD in transition education programs are controllable. Practice implication Further randomized studies are necessary to evaluate the impact of transition education program on quality of life, successful transfer to adult centre and, ultimately, prognosis.

Background Advances in congenital heart disease (CHD) have transferred the mortality from childhood to adulthood. Exercise capacity in young patients with CHD remains lower than in the general population, resulting in deconditioning and impaired quality of life. Evidence based-medicine in cardiac rehabilitation in this age group with CHD remains limited. We present the QUALI-REHAB study rationale, design and methods. Methods The QUALI-REHAB trial is a nationwide, multicentre, randomised, controlled study, aiming to assess the impact of a combined centre and home-based cardiac rehabilitation program on the quality of life of adolescents and young adults (13 to 25 years old) with CHD. Patients with a maximum oxygen uptake (VO2max) Conclusion After focusing on the survival in CHD, current research is opening on secondary prevention and patient-related outcomes. The QUALI-REHAB trial intends to assess if a combined centre and home-based rehabilitation program, could improve the quality of life and the exercise capacity in youth with CHD. Trial registration: Clinicaltrials.gov ( NCT03690518 ).

Interventional catheterization in children constantly improved these last decades to reach an extremely high success rate. However, the information given to parents before the intervention may be difficult and anxiety remains high. Aim We questioned about the impact of 3D cardiac printing on understanding, knowledge and anxiety of parents before interventional catheterization of their children. Methods Parents of children undergoing a percutaneous shunt closure were prospectively included. Two questionnaires were provided before and after the consultation: 1/a questionnaire of knowledge and understanding about the disease and the cardiac catheterization; 2/a self-report questionnaire to assess the anxiety (State-Trait Anxiety Inventory (STAI)). During the consultation, the ‘model group’ received an explanation of the children heart defect and the catheterization procedure using the 3D printed model of the cardiac lesion ( Fig. 1 ), while the ‘control group’ had the classical explanation with device and a manual drawing. Results Sixty three parents of 43 children were randomized in ‘control group’ (n = 31) or ‘model group’ (n = 32), including 6 ventricular septal defect, 23 patent ductus arteriosus and 34 atrial septal defect. At baseline, groups were comparable. The level of understanding and knowledge improved after the consultation in ‘control group’ and ‘model group’ (+5.5 ± 0.8 and +10,2 ± 0.8; P Conclusion 3D printed models improve knowledge and information deliverance in consultation for parents of children with CHD, and reduce their level of anxiety before cardiac catheterization

Loeys-Dietz syndrome is a rare form of connective tissue disorder, whose clinical features can resemble those of Marfan syndrome, but with a more unpolished appearance. Recently brought out, this pathology remains little known; however, its consequences may be dramatic. We report on the case of a 4-year-old girl followed for a congenital hip dislocation, in which a systematic exam found increased cutaneous elasticity and a bifid uvula, suggesting a connective tissue disorder. Symptoms were unpolished, as the child's height was normal, without any positive cardiac, rheumatological, or ophthalmological family history. Cardiovascular tests found a thoracic aortic aneurysm at the Valsalva sinus (26mm, Z-score=+4.24). A genetic investigation found a TGFβR2 gene mutation, leading to the diagnosis of Loeys-Dietz syndrome type 2. Skeletal damage associated with bifid uvula and/or hypertelorism and an aneurysm of the ascending aorta should guide the genetic investigation to the search for TGF-β vasculopathy such as Loeys-Dietz syndrome.

Background Accurate evaluation of the pulmonary valve (PV) is crucial before surgical repair of Tetralogy of Fallot (TOF). Aims To assess PV and pulmonary annulus (PA) morphology using three-dimensional (3D) transthoracic echocardiography (TTE) in infants referred for surgical repair of TOF. Also, to compare PA measurements obtained by 3D TTE with those from other imaging modalities, including two-dimensional (2D) TTE and computed tomography (CT), with reference to surgical measurements. Methods 3D zoom mode was used to assess PV morphology. 2D TTE and CT PA diameters were compared to both vertical and horizontal diameters obtained from 3D datasets. Surgical PA diameters were measured using Hegar's dilators. Results A total of 29 patients with TOF (median [range] age 6 [3–24] months) were included and all successfully underwent 2D and 3D TTE; 22 also underwent CT. The number of pulmonary leaflets could be visualized in 24 patients (82.8%), with complete concordance with surgical findings. Vertical diameter was significantly longer than horizontal diameter (P

A novel formulation of bosentan was evaluated in children with pulmonary arterial hypertension (PAH) in FUTURE-1, which characterized its pharmacokinetic and clinical profile. The subsequent phase III, open-label, long-term extension study, FUTURE-2, aimed to provide long-term tolerability, safety and exploratory efficacy data.Children (≥2 and12 years) with idiopathic or heritable PAH, who completed 12-week treatment in FUTURE-1 and for whom bosentan was considered beneficial were enrolled, and continued to receive bosentan 4 mg/kg twice-daily, which could be down-titrated to 2mg/kg if not tolerated. Safety and tolerability were evaluated via treatment-emergent adverse events (AEs), serious AEs, growth, and laboratory measurements. Exploratory efficacy endpoints included time to PAH worsening and long-term survival. All analyses were conducted on pooled data of both studies.36 patients were enrolled in FUTURE-1 and 33 continued in FUTURE-2. The overall median duration of exposure to bosentan was 27.7 (range 1.9-59.6) months. Treatment-emergent AEs occurred in 32 (88.9%) patients; AEs considered treatment-related in 15 (41.7%) patients. Of 51 serious AEs, three were considered treatment-related: two incidences of reported PAH worsening and one of autoimmune hepatitis. Six deaths occurred; none were considered treatment-related. Kaplan-Meier event-free estimates of PAH worsening were 78.9% and 73.6% at 2 and 4 years, respectively.The pediatric bosentan formulation was generally well tolerated, its safety profile comparable to that of the adult formulation when used in children. The results are in line with the efficacy profile of bosentan in previous pediatric and adult PAH studies of shorter duration.

Cardiac neonatal lupus syndrome is due to anti-SSA or SSB antibodies and mainly includes congenital heart block (CHB) and dilated cardiomyopathy (DCM). Its optimal management is still debated. We report a large series of autoimmune high degree CHB.Inclusion criteria in this retrospective study were fetuses or neonates with high-degree CHB associated with maternal anti-SSA/SSB antibodies.214 CHB were included: 202 detected in utero at a median term of 23 weeks' gestation (WG) [range 16 to 39 WG] and 12 neonatal cases diagnosed at a median age of 0 days [range birth to 8 days]. The 214 cases of CHB included 202 (94.4%) third-degree CHB, 8 (3.7%) second-degree CHB, and 4 (1.9%) intermittent CHB. In multivariate analysis, the factors associated with feto-neonatal deaths (15.7%) were hydrops (p0.001; hazard ratio [HR] 12.4 [95% confidence interval (95%CI) 4.7-32.7]) and prematurity (p=0.002; HR 17.1 [95%CI 2.8-103.1]). During a median follow-up of 7 years [birth to 36 years], 148 of 187 children born alive (79.1%) had a pacemaker, 35 (18.8%, one missing data) had DCM, and 22 (11.8%) died. In multivariate analysis, factors associated with child death were in utero DCM (p=0.0157; HR 6.37 [95%CI: 1.25-32.44]), postnatal DCM (p0.0001; HR 227.58[95%CI: 24.33-2128.46]) and pacemaker implantation (p=0.0035; HR 0.11[95%CI: 0.02-0.51]). The use of fluorinated steroids was neither associated with survival nor with regression of 2nd degree CHB.In this second largest series of CHB, we confirm some of the previous results. We were unable to find data supporting the routine use of in utero fluorinated steroids.

Summary Background In recent decades, advances in surgery and therapeutic catheterization have steadily increased the life expectancy and prevalence of adults with congenital heart disease (CHD). Aims We assessed medical and psychosocial variables of adults with CHD, according to the disease complexity. Methods We included, from a single-centre observational cohort study, 135 consecutive adults with CHD (median age of 40 years, interquartile range: 28.0–51.0) followed in our cardiology unit, who answered a questionnaire assessing daily activity and psychosocial functioning. Disease complexity was classified according to the Bethesda conference. Results Cardiac malformation complexity was simple in 61 (45.2%), moderate in 50 (37.0%) and complex in 24 (17.8%) patients. Cardiac surgery had been performed in 86.5% of moderate and complex patients. Complications (such as heart failure, arrhythmia and pulmonary hypertension) were mainly observed in the complex group ( P = 0.003). Physical activity was lower in the complex group (no activity in 58.8%, but sport previously contraindicated in 50% of these; P = 0.03). Education level tended to be lower in the complex and moderate groups than in the simple group (respectively, 31.2% and 33.3% vs. 45.7% had passed the Baccalaureate; P = 0.47). The pass rate was lower in patients with complications ( P = 0.037) or more than one cardiac surgery ( P = 0.03). In the complex group, 56.3% of patients were unemployed ( P = 0.048). Conclusions Complexity of heart disease and medical history affect education level and employment of adults with CHD. Academic education of children with a complex defect and career counselling are important to prevent unemployment among adults with CHD.

Introduction Teaching of congenital heart disease (CHD) through 3D printed models is feasible and useful as it improves learning. Medical students are highly satisfied with single defect CHD learning through 3D printing. Aim To evaluate the usefulness and degree of satisfaction with learning through 3D printed models in CHD with several associated defects, compared to a single defect CHD. Methods Students from 5th year of medicine attending a lecture in CoA (n = 118), VSD (n = 50) and TOF (n = 62) were randomised in 6 groups. During the lecture, 3D printed models of each CHD were presented and analysed by the students in the test group, same lecture without 3D models was performed for the control group for each CHD. Knowledge acquisition was obtained by pre and post-lecture test. Student's satisfaction and self-efficacy ratings were evaluated by the subjective post-lecture survey. Satisfaction between CHD groups was compared using Bonferroni method and test results between 3D & control group by t-test. Results Students in the multiple defect (ToF) group were less satisfied of 3D printed models than the students in the single defect (CoA & VSD) groups (P ˂ 0.01). After-lecture test scores for the groups attending the single defect CHD lectures were significantly higher for the students learning through 3D printed models (P = .04 in CoA group; P = 0.03 in VSD group). There was no difference in the post-lecture scores between the 3D learning and control groups attending the ToF lecture. Control ant test groups were comparable by age and sex ( Fig. 1 ). Conclusions Learning of complex CHD is challenging even with the most advanced educational techniques. Visual access to all the defects presented by the 3D model is necessary for correct understanding of the model. Transparent printing materials allow for the students to simulate the flow trajects with probes. In our experience, virtual 3D models can be a great resource and even more when analysed on virtual reality devices.

Imaging fusion between echocardiography and fluoroscopy was recently developed. The aim of this study was to assess its feasibility and accuracy during pediatric cardiac catheterization.Thirty-one patients (median weight, 26 kg; interquartile range [IQR], 21-37 kg) who underwent percutaneous atrial septal defect closure were prospectively included. The feasibility and accuracy of various imaging fusion modalities (live two-dimensional, live color two-dimensional, live three-dimensional and markers) with EchoNavigator software were assessed. To assess the accuracy of spatial registration of the echocardiogram on the fluoroscopic image, the occluder screw, an object that appeared on each image, was used as a reference tool, and the distance between the two when fused was measured. A distance was measured on the fusion screen between a marker positioned on the screw from the echocardiography screen and from the fluoroscopy screen (distance 1). Another distance was measured on the fusion screen between the screw visualized by three-dimensional echocardiography and by fluoroscopy (distance 2). The two distances were measured on four C-arm orientations in end-systolic and end-diastolic frames.Fusion and marker positioning were feasible in real time in all cases. On the fusion screen, median systolic and diastolic distance 1 were 0.5 mm (IQR, 0.3-1 mm) and 2 mm (IQR, 1.5-2.5 mm; P .0001), respectively. The marker positioned from the echocardiography screen was fixed on the fusion screen and did not follow the movement of the screw. Median systolic and diastolic distance 2 were 0.5 mm (IQR, 0-0.5 mm) and 2 mm (IQR, 1.5-2.5 mm; P .0001), respectively.Echocardiographic fluoroscopic imaging fusion is feasible, safe, and accurate in children weighting20 kg. This technique offers a new method of imaging guidance in the catheterization laboratory for complex procedures and training.

Summary Background Transoesophageal echocardiography (TOE) has become indispensable in the catheterization laboratory in the guidance of some percutaneous interventions, as a complementary imaging technique to fluoroscopy. However, the two imaging modalities are presented separately and differently, making interpretation of the anatomical spatial relationships complicated. EchoNavigator® (Philips Healthcare, Best, the Netherlands) is an innovative software package, enabling fusion of fluoroscopic and echocardiographic images on the same screen. Aims To assess the feasibility of EchoNavigator® in the guidance of interventional procedures, and to present our initial clinical experience with this software. Methods Children with congenital heart disease who underwent interventional catheterization needing guidance with TOE from December 2015 to December 2017 were included. TOE was realized using a X7-2t TOE probe (Philips Healthcare) connected to an echocardiographic system (EPIC™; Philips Healthcare, Andover, MA). Fluoroscopy was realized using the Allura Xper FD/10 system (Philips Healthcare). Image fusion was attempted in all patients using EchoNavigator®. Markers were positioned on the target zone on echocardiographic images, and projected onto the merged screen. Results Fifty-one children were included (mean age, 8 years; mean weight, 25 kg). Thirty-six patients underwent atrial septal defect closure, 10 ventricular septal defect closure, three aortic valve dilatation and two right ventricular outflow tract revalvulation. Image fusion was successfully obtained in all patients during all steps of the procedure. No complication related to the TOE probe was observed. Markers were successfully positioned in the all target zones, and were automatically projected onto the fusion screen. Conclusions The EchoNavigator® system is feasible and safe in the guidance of interventional catheterization in children with congenital heart disease; it enables better appreciation of anatomical relationships and improves the confidence of the interventionist.

Background Pathogenic variants in SMAD3 (type 3 LDS, Marfan-like connective tissue disorder) cause thoracic aortic aneurysms and dissections, along with aneurysms and rupture of other arteries. Generally, these aggressive vascular damages are associated with multisystemic signs including skeletal abnormalities and premature osteoarthritis. Variable expressivity and incomplete penetrance are commonly associated. Methods Aortic status, events, and clinical features were abstracted through retrospective review of medical records 20 new patients (28.8 years-old (6–60)) from 8 families from our Reference Centre. After a complete review of the literature, we collected a total of 49 unique variants of different nature (missense, truncating and splicing variants) from 152 individuals of 58 unrelated families. The aim of this study was to look for genotype-phenotype correlations between the mutations of this gene and the severity of the phenotype. Results Aortic aneurysm and/or dissection are the main vascular findings, affecting respectively 57% and 32% of all type 3 LDS patients described. In our cohort of patients, half presents an aortic dilatation (10/20), 10% an aortic dissection. Three of our patients displays an aortic dilatation during their childhood (at 8 and 7 years old and a surgery for an aortic dilation at 10 years old). Aneurysms and dissections can also be seen in other arteries in 27% (35/138) and particularly intracranial aneurysms found in 20% of patients (21/103), like in two of our patients, one presented an iliac artery dissection. Arterial tortuosity is also frequent, particularly in carotids, representing about a third of the patients (36/117 = 31%), 2 of our 8 patients. Conclusions SMAD3 pathogenic variants cause thoracic aortic aneurysms and dissections in the majority of individuals with variable age of onset and reduced penetrance. We confirmed that there is no correlation between the mutation type and the phenotype severity. Aneurysms-Osteoarthritis syndrome (AOS), genotype-phenotype correlation, heritable thoracic aortic aneurysms and dissections (hTAAD), Loeys-Dietz syndrome, SMAD3, Marfan-like connective tissue disorder, TGFβ pathway.

Introduction Understanding of cardiac structure has been improved by 3D cardiac echocardiography. The anatomy and geometry of the mitral valve annulus (MVA) has been previously described with advanced imaging techniques, allowing for a better comprehension of valve dysfunction and providing significant information for the surgical repair. Aim To apply transthoracic 3D echocardiography (3DTTE) for quantitative and qualitative assessment and comparison of the pathologic MVA in congenital cardiopathies (CC) of the valve with a normal group. Methods Patients with repaired atrioventricular septal defect (AVSD) attending consultation were prospectively included and matched with a control group of healthy children by sex, age and body surface area (BSA). 3DTTE full volume and 3D zoom acquisitions were performed on a Philips EPIQ7. The 3D shape of the annuli was reconstructed and analysed with TOMTEC™ 4D MV-ASSESSMENT© ( Fig. 1 ). The assessed and compared parameters were annular area (2D & 3D), circumference, high-low distances (height), anterolateral-posterolateral (ALPM), and anteroposterior (AP) axes, non-planar angle (NPA), sphericity index, angle between the aortic annulus and AP axe (AAoAP angle). All measurements were indexed by BSA. Results A total of 18 participants were recruited. Both groups were comparable in age (10.67 ± 3.45 years) and BSA (1.13 ± 0.27 m2). All acquisitions could be analysed with need of minimal editing of the annulus after automated detection, leaflets couldn’t be analysed in the AVSD group. Significative differences between both groups were found in the NPA with an increase in the nonplanarity for the patients with a repaired AVSD (144.5 vs. 132.9; P ˂ 0.01) and a more circular shape represented by a higher sphericity index (0.99 vs. 0,85; P = 0.01). No difference was found in indexed height, area and diameters were similar between both groups. Conclusions The specific and exclusive shape of the MVA in patients with repaired AVSD was revealed in the patients studied, resulting in a loss of the saddle shape structure. Those results could help in the comprehension of anatomic changes of the mitral valve annulus occurring after AVSD surgery.