Left Ventricular Longitudinal Strain Abnormalities in Childhood Exposure to Anthracycline Chemotherapy.

Current mortality is low in cases of childhood acute leukemia. Dilated cardiomyopathy induced by anthracyclines remains the main cause of morbidity and mortality during mid-term and long-term follow-up. The aim of our study was to analyze the profile of left ventricular alterations in children treated with anthracyclines and to analyze risks and protective factors, including physical activity. Children and young adults with acute leukemia treated with anthracyclines between 2000 and 2018 during childhood were included. The physical activity performed by the patients before and after treatment was quantified in metabolic equivalent tasks, MET.h, per week. An echocardiographic assessment was performed, including strain analysis. Thirty-eight patients with a median age of 5 [3-8] years were included. Dilated cardiomyopathy was diagnosed in 3 patients and longitudinal strain abnormalities were observed in 11 patients (28.9%). Radiotherapy, cumulative anthracycline doses > 240 mg/m2, and the practice of physical activity > 14 MET.h per week (after leukemia treatment) were independently associated with strain abnormalities. In multivariate analysis, radiotherapy was significantly associated with an increased risk of LV GLS abnormalities (OR = 1.26 [1.01-1.57], p = 0.036), and physical activity > 14 MET.h/week after oncological treatment was significantly associated with a reduction in the risk of LV GLS abnormalities (OR of 0.03 [0.002-0.411], p = 0.009). The strain assessment of left ventricular function is an interesting tool for patient follow-up after leukemia treatment. Moderate and steady physical activity seems to be associated with fewer longitudinal strain abnormalities in patients treated with anthracyclines during childhood.

Genetic profile and genotype-phenotype correlations in childhood cardiomyopathy.

BACKGROUND: Genetic cardiomyopathy is a rare disease in childhood. AIMS: To analyse clinical and genetic aspects of a paediatric cardiomyopathy population, and to establish genotype-phenotype correlations. METHODS: We performed a retrospective study of all patients with idiopathic cardiomyopathy aged<18years in Southeast France. Secondary causes of cardiomyopathy were excluded. All data (clinical, echocardiography, genetic testing) were collected retrospectively. Patients were classified into six groups: hypertrophic cardiomyopathy; dilated cardiomyopathy; restrictive cardiomyopathy; left ventricular non-compaction; arrhythmogenic right ventricular dysplasia; and mixed cardiomyopathy. Patients who did not have a complete genetic test according to current scientific developments had another deoxyribonucleic acid blood sample during the study time. Genetic tests were considered positive if the variant found was classified as pathogenic, likely pathogenic or a variant of uncertain significance. RESULTS: Eighty-three patients were included between 2005 and 2019. Most patients had hypertrophic cardiomyopathy (39.8%) or dilated cardiomyopathy (27.7%). The median age at diagnosis was 1.28years (interquartile range: 0.27-10.48years). Heart transplantation was performed in 30.1% of patients, and 10.8% died during follow-up. Among 64 patients with a complete genetic analysis, 64.1% had genetic anomalies, mostly in MYH7 (34.2%) and MYBPC3 (12.2%) genes. There were no differences in the whole cohort between genotype-positive and genotype-negative patients. In the hypertrophic cardiomyopathy group, 63.6% had a positive genetic test. Patients with a positive genetic test more often had extracardiac impact (38.1% vs. 8.3%; P=0.009), and more often required an implantable cardiac defibrillator (23.8% vs. 0%; P=0.025) or a heart transplant (19.1% vs. 0%; P=0.047). CONCLUSIONS: In our population, children with cardiomyopathy had a high positive genetic test rate. Hypertrophic cardiomyopathy with a positive genetic test is associated with a worse outcome.

Impact of cardiac surgical timing on the neurodevelopmental outcomes of newborns with Complex congenital heart disease (CHD).

Background: More than half of infants with complex congenital heart disease (CHD) will have a neurodevelopmental disorder of multifactorial causes. The preoperative period represents a time-window during which neonates with complex CHD are in a state of hypoxia and hemodynamic instability, which fosters the emergence of brain injuries and, thus, affects early brain networks and neurodevelopmental outcomes. Currently, there is no consensus regarding the optimal age for cardiac surgery in terms of neurodevelopmental outcomes, and its definition is a real challenge. Our aim is to determine the relationship between cardiac surgical timing and long-term neurodevelopmental outcomes for various types of complex CHD. Methods: We hypothesize that earlier surgical timing could represent a neuroprotective strategy that reduces perioperative white matter injuries (WMIs) and postoperative morbidity, leading to improved neurodevelopmental outcomes in infants with complex CHD. Firstly, our prospective study will allow us to determine the correlation between age at the time of surgery (days of life) and neurodevelopmental outcomes at 24 months. We will then analyze the correlation between age at surgery and (i) the incidence of WMIs (through pre- and postoperative MRIs), (ii) postoperative morbidity, and (iii) the duration of the hospital stay. Implications and Dissemination: This research protocol was registered in the Clinical Trial Registry (National Clinical Trial: NCT04733378). This project aims to help launch the first Neurocardiac Investigation Clinic in Marseille - AP-HM - to propose an overall personalized monitoring and treatment program for patients operated on for complex CHD.

Morphological analysis of ventricular septal defect by echocardiography for prediction of aortic regurgitation in pediatric population.

Ventricular septal defects (VSD) are the most common congenital heart diseases in children. Among them, perimembranous VSD (pm-VSD) have a higher risk of complications, including aortic valve prolapse and aortic regurgitation (AR). The aim of our study was to assess echocardiographic criteria associated with AR during follow-up of pm-VSD. Forty children with restrictive pm-VSD, followed-up in our unit and who underwent a workable echocardiographic evaluation between 2015 and 2019 were included and retrospectively analyzed. The propensity score was used to match 15 patients with AR to 15 patients without AR. Median age was 2.2 year [1.4-5.7]. Median weight was 14 kg [9.9-20.3]. Aortic annulus z-score, Valsalva sinus z-score, sinotubular junction z-score, valve prolapse and commissure commitment were significantly different between the two groups (p = 0.047, p = 0.001, p = 0.010, p = 0.007, p < 0.001 respectively). Aortic root dilatation, aortic valve prolapse and commissure commitment to a perimembranous VSD are associated to aortic regurgitation.

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.

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.

Anterograde blood flow associated with modified Blalock-Taussig shunt does not modify pulmonary artery growth compared with modified Blalock-Taussig shunt alone.

BACKGROUND: The main difference between extreme tetralogy of Fallot (TOF) and pulmonary atresia with ventricle septal defect (PA/VSD) is anterograde pulmonary blood flow (APBF). It is speculated that the association of modified Blalock-Taussig shunt (mBTS) with APBF favours shunt thrombosis, but promotes better pulmonary artery growth. AIM: To compare pulmonary artery growth after mBTS between TOF and PA/VSD. METHODS: From 1995 to 2018, 77 mBTS procedures were performed in infants (aged<1 year): 45 for TOF; 32 for PA/VSD. Using a 1/1 propensity score-matched analysis, 38 patients were included (19 per group). Delta Nakata was defined as the difference in the Nakata index before biventricular repair and before mBTS. RESULTS: After matching, the preoperative Nakata index was similar in the two groups (TOF 101±34 vs. PA/VSD 106±35 mm2/m2; P=0.75). Age and weight were similar (TOF 24±20 days, 3.3±0.6kg vs. PA/VSD 24±33 days, 3.3±0.9kg; P=0.84 and P=0.77, respectively). There was no difference in rates of in-hospital mortality (TOF 0% vs. PA/VSD 10%; P=0.13) or mBTS thrombosis (TOF 15% vs. PA/VSD 10%; P=0.63). The left and right pulmonary artery diameters at time of biventricular repair were similar (TOF 7.5±2.2 and 6.7±2.1 vs. PA/VSD 8±2.7 and 7.1±2.5mm; P=0.43 and P=0.78, respectively), as were delta Nakata (TOF 112±102 vs. PA/VSD 107±66 mm2/m2; P=0.89), median age for biventricular repair (P=0.83) and reintervention rates (TOF 10% vs. PA/VSD 15%; P=0.67). CONCLUSIONS: We found no difference in pulmonary artery growth between APBF with mBTS versus mBTS alone. Thus, we could not show an increase in mBTS thrombosis with APBF.

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.

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.

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.

Parental anxiety before invasive cardiac procedure in children with congenital heart disease: Contributing factors and consequences.

OBJECTIVE: Medical information provided to parents of a child with a congenital heart disease can induce major stress. Visual analog scales have been validated to assess anxiety in the adult population. The aim of this study was to analyze parental anxiety using a visual analog scale and to explore the influencing factors. DESIGN: This prospective cross-sectional study. SETTING: Tertiary care regional referral center for congenital heart disease of Marseille-La Timone university hospital. PATIENTS: Parents of children with a congenital heart disease, as defined by the ACC-CHD classification, referred for cardiac surgery or interventional cardiac catheterization, were offered to participate. INTERVENTION AND OUTCOME MEASURE: The parental level of anxiety was assessed using a visual analog scale (0-10) before intervention and after complete information given by the cardiologist, the surgeon or the anesthetists. RESULTS: Seventy-three children [7 days-13 years], represented by 49 fathers and 71 mothers, were included in the study. A total of 42 children required cardiac surgery and 31 children underwent interventional cardiac catheterization. The mean score of maternal anxiety was significantly higher than the paternal anxiety (8.2 vs 6.3, P < .01). A high level of maternal anxiety (visual analog scale > 8) was associated with paternal anxiety (P = .02), the child's comorbidity (P = .03), the distance between home and referral center (P = .04), and the level of risk adjustment for congenital heart surgery (P = .01). In multivariate analysis, maternal anxiety was associated with paternal anxiety (OR = 4.9; 95% confidence interval [1.1-19.2]), and the level of risk adjustment for congenital heart surgery (OR = 11.4; 95% confidence interval [1.2-116.2]). No significant association was found between parental anxiety and prenatal diagnosis. CONCLUSION: This study highlighted several factors associated with the parental anxiety. Identifying the parents at risk of high stress can be useful to set up psychological support during hospitalization.

Mobile extracorporeal membrane oxygenation for children: single-center 10 years' experience.

OBJECTIVES: Extracorporeal membrane oxygenation has become a gold standard in treatment of severe refractory circulatory and/or pulmonary failure. Those procedures require gathering of competences and material. Therefore, they are conducted in a limited number of reference centers. Emergent need for such treatments induces either hazardous transfers or a mobile pediatric extracorporeal membrane oxygenation team able to remote implantation and transportation. The aim of this work is not to focus on pediatric extracorporeal membrane oxygenation outcomes or indications, which have been extensively discussed in the literature. This study would like to detail the implementation, safety, and feasibility, even in a middle-size pediatric cardiac surgery reference center. PATIENTS: This is a retrospective analysis of a series of patients initiated on extracorporeal membrane oxygenation in a peripheral center and transferred to a reference center. The data were collected from 10 consecutive years: from 2006 to 2016. RESULTS: A total of 57 pediatric patients with a median weight of 6.00 (3.2-14.5) kg and median age of 2.89 (0.11-37.63) months were cannulated in peripheral center and transported on extracorporeal membrane oxygenation. We did not experience any adverse event during transport. The outcomes were comparable to our literature-reported on-site extracorporeal membrane oxygenation series with 42 patients (74%) weaned from extracorporeal membrane oxygenation and a 30-day survival of 60%. Neither patient's age nor weight, indication for extracorporeal membrane oxygenation or length of transport, was statistically significant in terms of outcomes. CONCLUSION: Offsite extracorporeal membrane oxygenation implantation and ground or air transport for pediatric patients on extracorporeal membrane oxygenation appeared to be safe when performed by a dedicated and experienced team, even within a mid-size center.

Impact of education and training course for ECMO patients based on high-fidelity simulation: a pilot study dedicated to ICU nurses.

INTRODUCTION: Medical and para-medical education is one of the key points of healthcare strategy. Training and education based on high-fidelity simulation is one of the gold standards in modern healthcare institutions. We describe a model of training dedicated to ICU nurses in charge of patients with ECMO. The aim of our educational tool was to teach ICU nurses ECMO basic knowledge and skills. METHODS: An ECMO Specialist Course Committee implemented the training programme. It was on two consecutive days and consisted of theoretical, practical and high-fidelity, simulation-based teaching. A content expert implemented each scenario and learning objectives were defined. Participants were assessed pre- and post-test (Group 1 and Group 2). RESULTS: In two years, seven sessions took place and 40 volunteers were enrolled. High-fidelity, simulation-based teaching consisted of seven scenarios. There was a significant improvement in mean score between pre- and post-test. Moreover, we noticed that the basic level (pre-test) of participants was improving over the time. The mean pre-test scores of Group 2 were significantly higher than Group1. CONCLUSION: The implementation of education and training course for ICU nurses in charge of patients on ECMO is feasible and reliable. It improves nurse personal levels, but also shares in improving the global level of the team to which they belong.

Stenting right ventricular outflow in an infant with tetralogy of Fallot and well-developed pulmonary arteries.

A right ventricular outflow tract stent was implanted in a 1-month-old (3.5 kg) baby boy with tetralogy of Fallot and worsening cyanosis to relieve infundibular and pulmonary valve stenosis in the setting of well-developed pulmonary artery branches. This management allowed a symmetric and optimal growth of the pulmonary artery branches, with right and left pulmonary arteries measuring 7-mm (z-score, +1.3 SD) and 7.3-mm (z-score, +1.7 SD), respectively, 3 months after stent implantation. No signs of pulmonary overcirculation developed, and complete surgical repair was performed at the age of 6 months.

Multiple mycotic aneurysms reveal Staphylococcus lugdunensis endocarditis in a young patient.

Mycotic aneurysms are rare, and depending on their location, can threaten functional prognosis. We report on a 17-year-old girl with no previous history of cardiovascular or infectious disease, referred to our Department of Cardiology with right hemiplegia and aphasia. A neurological evaluation revealed thrombosis of a mycotic cerebral aneurysm, complicated by ischemic and hemorrhagic infarction. Transthoracic echocardiography indicated huge, highly mobile mitral vegetation associated with a mitral regurgitation with a triple stream. Hemocultures isolated Staphylococcus lugdunensis. Shortly afterward, she developed bilateral tibial and pedal mycotic aneurysm. The patient received antibiotics, with minor neurological improvement initially, but she soon died because of a brain herniation. Based on our findings in this case, we discuss the features of endocarditis attributable to S. lugdunensis.