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.

Expanding the phenome and variome of the ROBO-SLIT pathway in congenital heart defects: toward improving the genetic testing yield of CHD.

BACKGROUND: Recent studies have shown the implication of the ROBO-SLIT pathway in heart development. Within this study, we aimed to further assess the implication of the ROBO and SLIT genes mainly in bicuspid aortic valve (BAV) and other human congenital heart defects (CHD). METHODS: We have analyzed a cohort of singleton exome sequencing data comprising 40 adult BAV patients, 20 pediatric BAV patients generated by the Pediatric Cardiac Genomics Consortium, 10 pediatric cases with tetralogy of Fallot (ToF), and one case with coarctation of the aorta. A gene-centered analysis of data was performed. To further advance the interpretation of the variants, we intended to combine more than 5 prediction tools comprising the assessment of protein structure and stability. RESULTS: A total of 24 variants were identified. Only 4 adult BAV patients (10%) had missense variants in the ROBO and SLIT genes. In contrast, 19 pediatric cases carried variants in ROBO or SLIT genes (61%). Three BAV patients with a severe phenotype were digenic. Segregation analysis was possible for two BAV patients. For the homozygous ROBO4: p.(Arg776Cys) variant, family segregation was consistent with an autosomal recessive pattern of inheritance. The ROBO4: c.3001 + 3G > A variant segregates with the affected family members. Interestingly, these variants were also found in two unrelated patients with ToF highlighting that the same variant in the ROBO4 gene may underlie different cardiac phenotypes affecting the outflow tract development. CONCLUSION: Our results further reinforce the implication of the ROBO4 gene not only in BAV but also in ToF hence the importance of its inclusion in clinical genetic testing. The remaining ROBO and SLIT genes may be screened in patients with negative or inconclusive genetic tests.

Lympho-hematopoietic malignancies risk after exposure to low dose ionizing radiation during cardiac catheterization in childhood.

Pediatric patients with congenital heart disease (CHD) often undergo low dose ionizing radiation (LDIR) from cardiac catheterization (CC) for the diagnosis and/or treatment of their disease. Although radiation doses from a single CC are usually low, less is known about the long-term radiation associated cancer risks. We aimed to assess the risk of lympho-hematopoietic malignancies in pediatric CHD patients diagnosed or treated with CC. A French cohort of 17,104 children free of cancer who had undergone a first CC from 01/01/2000 to 31/12/2013, before the age of 16 was set up. The follow-up started at the date of the first recorded CC until the exit date, i.e., the date of death, the date of first cancer diagnosis, the date of the 18th birthday, or the 31/12/2015, whichever occurred first. Poisson regression was used to estimate the LDIR associated cancer risk. The median follow-up was 5.9 years, with 110,335 person-years. There were 22,227 CC procedures, yielding an individual active bone marrow (ABM) mean cumulative dose of 3.0 milligray (mGy). Thirty-eight incident lympho-hematopoietic malignancies were observed. When adjusting for attained age, gender and predisposing factors to cancer status, no increased risk was observed for lympho-hematopoietic malignancies RR/mGy = 1.00 (95% CI: 0.88; 1.10). In summary, the risk of lympho-hematopoietic malignancies and lymphoma was not associated to LDIR in pediatric patients with CHD who undergo CC. Further epidemiological studies with greater statistical power are needed to improve the assessment of the dose-risk relationship.

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.

Early Presentation of Patients with Abnormal Origin of Left Coronary Artery from the Pulmonary Artery is a Predictor of Poor Mid-term Outcomes.

Abnormal origin of left coronary artery from the pulmonary artery (ALCAPA) is one of the most common causes of myocardial ischemia and infarction in childhood. This study aimed to determine the correlation between age at clinical presentation, level of ventricular dysfunction, and post-repair outcomes. This is retrospective study from 1993 to 2018 including thirty-one patients. The study cohort was divided into two groups according to age (< 6 months, > 6 months). The significance level was set at p 0.05.The median follow-up time was 72 [24-168] months. Median age was 4.7 [2.3-16] months. Median weight was 6.2 [4.3-9] kg. There was severe left ventricular (LV) dysfunction (ejection fraction < 35%) in 64.5% of patients. Mitral regurgitation (MR) was moderate to severe in 13 patients (41.9%). Two patients (6.4%) required extracorporeal membrane oxygenation (ECMO) support before surgery and 6 (19.4%) after correction. Age < 6 months was significantly associated with severe clinical presentation, severe LV dysfunction, delayed sternal closure, prolonged respiratory mechanical support, and prolonged length of ICU stay (p = 0.024, p = 0.042, p = 0.002, p = 0.042, p = 0.022, respectively). After surgery, ejection fraction improved to a median of 57% [50.7-60.5]. MR regressed in 12 patients (92.3%). Mortality rate after surgery was 9.7%. All patients were free from reoperation at the last follow-up. Young age at diagnosis was significantly associated with a more severe clinical presentation and poorer outcomes. After re-establishment of a two-coronary circulation, both ventricular function and MR tend to normalize over time regardless of age at repair.

Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy-analysis of registry data.

AIMS: To estimate the effect of prophylactic angiotensin-converting enzyme inhibitors (ACEi) on survival in Duchenne muscular dystrophy (DMD). METHODS AND RESULTS: We analysed the data from the French multicentre DMD Heart Registry (ClinicalTrials.gov: NCT03443115). We estimated the association between the prophylactic prescription of ACEi and event-free survival in 668 patients aged 8 to 13 years, with normal left ventricular function, using (i) a Cox model with intervention as a time-dependent covariate, (ii) a propensity-based analysis comparing ACEi treatment vs. no treatment, and (iii) a set of sensitivity analyses. The study outcomes were overall survival and hospitalizations for heart failure (HF) or acute respiratory failure. Among the 668 patients included in the DMD Heart Registry, 576 (mean age 6.1 ± 2.8 years) were eligible for this study, of whom 390 were treated with ACEi prophylactically. Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with ACEi, respectively. In a Cox model with intervention as a time-dependent variable, the hazard ratio (HR) associated with ACEi treatment was 0.49 [95% confidence interval (CI) 0.34-0.72] and 0.47 (95% CI 0.31-0.17) for overall mortality after adjustment for baseline variables. In the propensity-based analysis, 278 patients were included in the treatment group and 834 in the control group, with 18.5% and 30.4% 12-year estimated probability of death, respectively. ACEi were associated with a lower risk of death (HR 0.39; 95% CI 0.17-0.92) and hospitalization for HF (HR 0.16; 95% CI 0.04-0.62). All other sensitivity analyses yielded similar results. CONCLUSION: Prophylactic ACEi treatment in DMD was associated with a significantly higher overall survival and lower rates of hospitalization for HF.

Dilated-Left Ventricular Non-Compaction Cardiomyopathy in a Pediatric Case with SPEG Compound Heterozygous Variants.

Left Ventricular Non-Compaction (LVNC) is defined by the triad prominent myocardial trabecular meshwork, thin compacted layer, and deep intertrabecular recesses. LVNC associated with dilation is characterized by the coexistence of left ventricular dilation and systolic dysfunction. Pediatric cases with dilated-LVNC have worse outcomes than those with isolated dilated cardiomyopathy and adult patients. Herein, we report a clinical and genetic investigation using trio-based whole-exome sequencing of a pediatric case with early-onset dilated-LVNC. Compound heterozygous mutations were identified in the Striated Muscle Enriched Protein Kinase (SPEG) gene, a key regulator of cardiac calcium homeostasis. A paternally inherited mutation: SPEG; p.(Arg2470Ser) and the second variant, SPEG; p.(Pro2687Thr), is common and occurred de novo. Subsequently, Sanger sequencing was performed for the family in order to segregate the variants. Thus, the index case, his father, and both sisters carried the SPEG: p.(Arg2470Ser) variant. Only the index patient carried both SPEG variants. Both sisters, as well as the patient's father, showed LVNC without cardiac dysfunction. The unaffected mother did not harbor any of the variants. The in silico analysis of the identified variants (rare and common) showed a decrease in protein stability with alterations of the physical properties as well as high conservation scores for the mutated residues. Interestingly, using the Project HOPE tool, the SPEG; p.(Pro2687Thr) variant is predicted to disturb the second fibronectin type III domain of the protein and may abolish its function. To our knowledge, the present case is the first description of compound heterozygous SPEG mutations involving a de novo variant and causing dilated-LVNC without neuropathy or centronuclear myopathy.

Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic.

BACKGROUND: Cardiac injury and myocarditis have been described in adults with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children as defined by the US Centers for Disease Control and Prevention. METHODS: Over a 2-month period, contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. RESULTS: Thirty-five children were identified and included in the study. Median age at admission was 10 years (range, 2-16 years). Comorbidities were present in 28%, including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was <30% in one-third; 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation. Inflammation markers were suggestive of cytokine storm (interleukin-6 median, 135 pg/mL) and macrophage activation (D-dimer median, 5284 ng/mL). Mean BNP (B-type natriuretic peptide) was elevated (5743 pg/mL). Thirty-one of 35 patients (88%) tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. All patients received intravenous immunoglobulin, with adjunctive steroid therapy used in one-third. Left ventricular function was restored in the 25 of 35 of those discharged from the intensive care unit. No patient died, and all patients treated with extracorporeal membrane oxygenation were successfully weaned. CONCLUSIONS: Children may experience an acute cardiac decompensation caused by severe inflammatory state after SARS-CoV-2 infection (multisystem inflammatory syndrome in children). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

Dilatation of the aorta in children with advanced chronic kidney disease.

BACKGROUND: The peculiarity of the cardiovascular risk profile with increased arterial vulnerability is well known in adults with chronic kidney disease (CKD). It is explained by an increased incidence of traditional cardiovascular risk factors together with other comorbidities related to the uremic condition and cardiorenal syndrome (CRS). The present study aimed to determine the cardiovascular impact of the uremic condition in a pediatric population with advanced CKD. METHODS: From 2016 to 2018, 39 consecutive patients with advanced CKD who underwent echocardiographic evaluation were included. All echocardiographic examinations were performed by the same operator (FE). Demographic, clinical, biological, and echocardiographic data were collected. RESULTS: The mean age at echocardiographic exam was 9.7 ± 4.6 years. Twenty-four (61.5%) patients were on hemodialysis; 17 (43.6%) patients were in a peritoneal dialysis program of whom 11 switched at a later stage to hemodialysis. Eight (20.5%) patients had an arteriovenous fistula (AVF). Hypertension was present in 30 (76.9%) patients while left ventricular hypertrophy (LVH) was described in 13 (33.3%) patients. Dilatation of the ascending aorta (Z-score > 2) was found in 15 (38.4%) patients and was statistically (in univariate analysis) related to gender, hypertension, the presence of an AVF, and the use of hemodialysis after peritoneal dialysis (p = 0.024, p = 0.016, p = 0.006, p = 0.009, respectively). CONCLUSION: In addition to classical and predictable abnormalities related to CKD, we found a high prevalence of dilatation of the ascending aorta in children with advanced CKD. Hypertension, AVF, and hemodialysis were associated factors.

Myocardial infarct late after Fontan-type surgery in pulmonary atresia and intact ventricular septum: a must-know complication! About a case report.

Coronary abnormalities are frequent in pulmonary atresia and intact ventricular septum, mainly in patients with a very diminutive right ventricle. They severely impact on early and late prognosis. We describe an 8-year-old girl who presented with myocardial ischaemia, late after uneventful Fontan completion. The importance of precise delineation of the coronary anatomy upon initial assessment and during follow-up is emphasised.

Cardiovascular events in perimembranous ventricular septal defect with left ventricular volume overload: a French prospective cohort study (FRANCISCO).

The long-term prospective multi-centre nationwide (French) observational study FRANCISCO will provide new information on perimembranous ventricular septal defect with left ventricular overload but no pulmonary hypertension in children older than 1 year. Outcomes will be compared according to treatment strategy (watchful waiting, surgical closure, or percutaneous closure) and anatomic features of the defect. The results are expected to provide additional guidance about the optimal treatment of this specific population, which is unclear at present. BACKGROUND: The management of paediatric isolated perimembranous ventricular septal defect (pmVSD) with left ventricle (LV) volume overload but no pulmonary arterial hypertension (PAH) remains controversial. Three therapeutic approaches are considered: watchful waiting, surgical closure, and percutaneous closure. We aim to investigate the long-term outcomes of these patients according to anatomic pmVSD characteristics and treatment strategy. METHODS: The Filiale de Cardiologie Pediatrique et Congénitale (FCPC) designed the FRANCISCO registry, a long-term prospective nationwide multi-centre observational cohort study sponsored by the French Society of Cardiology, which enrolled, over 2 years (2018­2020), patients older than 1 year who had isolated pmVSD with LV volume overload. Prevalent complications related to pmVSD at baseline were exclusion criteria. Clinical, echocardiographic, and functional data will be collected at inclusion then after 1, 5, and 10 years. A core lab will analyse all baseline echocardiographic data to depict anatomical pmVSD features. The primary outcome is the 5-year incidence of cardiovascular events (infective endocarditis, sub-aortic stenosis, aortic regurgitation, right ventricular outflow tract stenosis, tricuspid regurgitation, PAH, arrhythmia, stroke, haemolysis, heart failure, or death from a cardiovascular event). We plan to enrol 200 patients, given the 10% estimated 5-year incidence of cardiovascular events with a 95% confidence interval of ±5%. Associations linking anatomical pmVSD features and treatment strategy to the incidence of complications will be assessed. CONCLUSIONS: The FRANSCICO study will provide the long-term incidence of complications in patients older than 1 year with pmVSD and LV volume overload. The results are expected to improve guidance for treatment decisions.

Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.

Berlin Heart EXCOR Paediatric Ventricular Assist Device: Does Weight Matter?

BACKGROUND: Berlin Heart EXCOR (BH) ventricular assist devices provide mechanical long-term circulatory support in children with end-stage heart failure, as a bridge to transplantation or to recovery. Most studies are from large-volume paediatric cardiac centres. AIM: The aim of this study was to analyse the experiences of three French centres and to compare these with available published data. METHOD: We performed a retrospective observational study of three paediatric cardiac intensive care units. All children supported with BH devices were included. Morbidity and mortality data were collected and risk factors analysed. RESULTS: Fifty-four (54) patients (54% male) were included. Survival rate was 73% while on a BH device. Median age at BH device implantation was 17 months (range 2-180 months). The predominant indication was dilated cardiomyopathy (61%). Bi-ventricular assist device was used in 25 (46%) cases. The total length of long-term circulatory support was 3,373 days, with a mean length per patient of 62.5 days (range 5-267 days). Thirty-two (32) patients were transplanted (59%) and seven (13%) were successfully weaned. Type and length of support did not influence morbidity. Main complications were renal dysfunction (57%), bleeding (41%), and infection (39%). In multivariate analysis, a weight <5 kg was significantly associated with higher mortality. CONCLUSIONS: The weight seems to be the most important risk factor of mortality in this precarious condition.

Phenotype and outcome of pulmonary arterial hypertension patients carrying a TBX4 mutation.

INTRODUCTION: TBX4 mutation causes small patella syndrome (SPS) and/or pulmonary arterial hypertension (PAH). The characteristics and outcomes of PAH associated with TBX4 mutations are largely unknown. METHODS: We report the clinical, functional, radiologic, histologic and haemodynamic characteristics and outcomes of heritable PAH patients carrying a TBX4 mutation from the French pulmonary hypertension (PH) network. RESULTS: 20 patients were identified in 17 families. They were characterised by a median age at diagnosis of 29 years (0-76 years) and a female to male ratio of three. Most of the patients (70%) were in New York Heart Association (NYHA) functional class III or IV with a severe haemodynamic impairment (median pulmonary vascular resistance (PVR) of 13.6 (6.2-41.8) Wood units). Skeletal signs of SPS were present in 80% of cases. Half of the patients had mild restrictive or obstructive limitation and diffusing capacity of the lung for carbon monoxide (D LCO) was decreased in all patients. High-resolution computed tomography (HRCT) showed bronchial abnormalities, peri-bronchial cysts, mosaic distribution and mediastinal lymphadenopathies. PAH therapy was associated with significant clinical improvement. At follow-up (median 76 months), two patients had died and two had undergone lung transplantation. One-year, three-year and five-year event-free survival rates were 100%, 94% and 83%, respectively. Histologic examination of explanted lungs revealed alveolar growth abnormalities, major pulmonary vascular remodelling similar to that observed in idiopathic pulmonary arterial hypertension (IPAH) and accumulation of cholesterol crystals within the lung parenchyma. CONCLUSION: PAH due to TBX4 mutations may occur with or without skeletal abnormalities across a broad age range from birth to late adulthood. PAH is usually severe and associated with bronchial and parenchymal abnormalities.

SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020.

End of April 2020, French clinicians observed an increase in cases presenting with paediatric inflammatory multisystem syndrome (PIMS). Nationwide surveillance was set up and demonstrated temporospatial association with the coronavirus disease (COVID-19) epidemic for 156 reported cases as at 17 May: 108 were classified as confirmed (n = 79), probable (n = 16) or possible (n = 13) post-COVID-19 PIMS cases. A continuum of clinical features from Kawasaki-like disease to myocarditis was observed, requiring intensive care in 67% of cases.

Acquired systemic-to-pulmonary shunts in a 6-month-old child: case report and review of the literature.

The incidence of paediatric venous thromboembolism has steadily increased in the past decade, by nearly 10% per year. Deep venous thrombosis may remain completely asymptomatic during the acute phase and symptoms may occur later, due to complications. We related the case of a 9-month-old child with increasing cyanosis. A computed tomography (CT) angiography showed a thrombosis of the superior vena cava (SVC) with the development of collateral flow from the systemic to the pulmonary veins. Transcatheter shunt occlusion after SVC recanalization was successfully performed. We discussed the characteristics of these cases and the consequence on our practice in term of treatment (anticoagulation, transcatheter, intervention) and screening.

Pulmonary atresia with ventricular septal defect and tetralogy of Fallot: transannular path augmentation versus systemic to pulmonary artery shunt for first-stage palliation.

BACKGROUND: Pulmonary atresia with ventricular septal defect and severe tetralogy of Fallot require a palliative procedure for pulmonary artery rehabilitation. For first-stage palliation, two main surgical options are still debated: right ventricle to pulmonary artery connection and modified Blalock-Taussig shunt. We compared the clinical outcomes of the two procedures. METHODS: From 1995 to 2018, 88 patients needed palliation (pulmonary atresia with ventricular septal defect n = 47; tetralogy of Fallot n = 41). Among these patients, 70 modified Blalock-Taussig shunt and 18 transannular path augmentation were performed before 6 months of age. Using a 1:1 propensity score match analysis, 20 patients were included in the analysis. The primary outcome was in-hospital mortality and pulmonary artery growth. RESULTS: After matching, the pre-operative Nakata was smaller in transannular path augmentation 54 ± 24 mm2/m2 than modified Blalock-Taussig shunt 109 ± 31 mm2/m2 (p < 0.001). The age and weight were similar (p = 0.31 and p = 0.9, respectively). There was no difference in in-hospital mortality (p = 0.3). The Nakata index before biventricular repair and delta Nakata were smaller in modified Blalock-Taussig shunt group (206 ± 80 mm2/m2, 75 ± 103 mm2/m2) than transannular path augmentation (365 ± 170 mm2/m2, 214 ± 165 mm2/m2; p = 0.03; p < 0.001). Median time to biventricular repair was similar (p = 0.46). The rate of interstage reintervention was similar (p = 0.63). CONCLUSIONS: The transannular path augmentation is better for the rehabilitation of the native pulmonary artery. Despite a smaller pulmonary artery, right ventricle to pulmonary artery connection is equivalent to modified Blalock-Taussig shunt for rate of biventricular repair and time to biventricular repair.

FOXC1 haploinsufficiency due to 6p25 deletion in a patient with rapidly progressing aortic valve disease.

6p25 deletion is a rare but well-known entity. The main clinical features include an abnormal facial appearance, developmental delay, and ocular anomalies. Cardiac anomalies are frequently seen but remain poorly delineated. We describe a 4-year-old girl with 6p25.3 deletion, which includes the FOXC1 gene, typical dysmorphic features associated with developmental delay and oculo-motor anomalies. Aortic valve dysplasia was diagnosed early in life. The cardiac lesion progressed very rapidly between the age of 3 and 4 years requiring aortic valve replacement. Genomic analysis of blood and excised valve tissue showed down-regulation of FOXC1 but also FOXC2 expression in the diseased aortic valve. This allows us to speculate on the potential role of FOXC1 in aortic valve anomalies.

Pulmonary Hypertension in the Preterm Infant with Chronic Lung Disease can be Caused by Pulmonary Vein Stenosis: A Must-Know Entity.

Pulmonary hypertension (PHT) in the preterm infant is frequently due to chronic lung disease. Rarely, PHT can be caused by pulmonary vein (PV) stenosis that has been described to be associated with prematurity. This study is a retrospective analysis of all premature infants <37 weeks of gestation with PV stenosis and PHT in two French pediatric congenital cardiac centers from 1998 till 2015. Diagnosis, hemodynamics and outcome are described. Sixteen patients met the inclusion criteria. Median gestational age was 28 weeks (25 + 6-35) with a median birth weight of 842 g (585-1500). The majority of infants (87.5 %) had chronic lung disease and associated cardiac defects. Median age at diagnosis was 6.6 months (1.5-71). Fifty-six percentage (n = 9) had initially unilateral PV stenosis affecting in 89 % the left PV. Median initial invasive mean pulmonary artery pressure was 42 mmHg (25-70). Treatment options included surgical intervention (n = 6), interventional cardiac catheter (n = 3) and/or targeted therapy for pulmonary arterial hypertension (n = 5). In six patients, decision of nonintervention was taken. Global mortality was 44 %. All deaths occurred within 7 months after diagnosis regardless of chosen treatment option. Mean follow-up was 6 years (4.9 months-12 years). At last visit, all eight survivors were in stable clinical condition with five of them receiving targeted therapy for pulmonary arterial hypertension. PV stenosis is an unusual cause of PHT in the premature infant with chronic lung disease. Diagnosis is challenging since initial echocardiography can be normal and the disease is progressive. Treatment options are numerous, but prognosis remains guarded.

Challenges of treatment of aortic obstruction in Takayasu disease.

Diffuse aortitis, as seen in Takayasu disease, is characterised by extreme wall fragility, associated with a high risk of complications such as dissection and aneurysm formation, following endovascular treatment. We report a patient with Takayasu disease who presented with a very difficult clinical course associated with several unfavourable outcomes of stent insertion.