Impact of COVID-19 disease on clinical research in pediatric and congenital cardiology.

BACKGROUND: COVID-19 triggered an unprecedented crisis affecting society at every level. Research in pediatric and congenital cardiology is currently in full development and may have been disrupted. The aim of the study was to determine the impact of COVID-19 on pediatric and congenital cardiology clinical research and to analyze decision-making and adaptation processes, from a panel of ongoing 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 pediatric and congenital cardiology centers. Investigators and clinical research assistants from each participating research center completed an online survey questionnaire, and each principal investigator underwent a 1-h web-based videoconference interview. RESULTS: A total of 34 study questionnaires were collected, reporting that 18 studies were totally suspended. Upon the 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 that in 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. CONCLUSION: The impact of the COVID-19 pandemic on clinical research in pediatric 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.

Late infective endocarditis after transcatheter tricuspid valve-in-valve implantation: A pediatric case report.

In patients with congenital heart diseases, new procedures, such as transcatheter valve replacement, have been associated with a non-negligible incidence of infective endocarditis (IE): up to 4% patient-year IE incidence. Prosthetic IE after percutaneous tricuspid valve replacement (PTVR) has been scarcely reported. We report the first pediatric case of IE after percutaneous tricuspid Melody™ valve-in-valve implantation in a boy who was diagnosed with Eisenmenger syndrome, related to patent ductus arteriosus. This first pediatric case of late IE (4 years) after PTVR is added to eight previously reported cases of IE from the valve-in-valve international database registry (VIVID registry).

Respiratory syncytial virus-associated mortality in a healthy 3-year-old child: a case report.

BACKGROUND: Respiratory syncytial virus (RSV) is the most frequently identified pathogen in children with acute lower respiratory tract infection. Fatal cases have mainly been reported during the first 6 months of life or in the presence of comorbidity. CASE PRESENTATION: A 47-month-old girl was admitted to the pediatric intensive care unit following sudden cardiopulmonary arrest occurring at home. The electrocardiogram showed cardiac asystole, which was refractory to prolonged resuscitation efforts. Postmortem analyses detected RSV by polymerase chain reaction in an abundant, exudative pericardial effusion. Histopathological examination was consistent with viral myoepicarditis, including an inflammatory process affecting cardiac nerves and ganglia. Molecular analysis of sudden unexplained death genes identified a heterozygous mutation in myosin light chain 2, which was also found in two other healthy members of the family. Additional expert interpretation of the cardiac histology confirmed the absence of arrhythmogenic right ventricular dysplasia or hypertrophic cardiomyopathy. CONCLUSIONS: RSV-related sudden death in a normally developing child of this age is exceptional. This case highlights the risk of extrapulmonary manifestations associated with this infection, particularly arrhythmia induced by inflammatory phenomena affecting the cardiac autonomic nervous system. The role of the mutation in this context is uncertain, and it is therefore necessary to continue to assess how this pathogenic variant contributes to unexpected sudden death in childhood.

Chikungunya disease among infants in French West Indies during the 2014 outbreak.

BACKGROUND: We aimed to describe the clinical and laboratory features of Chikungunya disease in infants aged from 1 month to 2years. METHODS: This epidemiologic study was carried out at the Pointe-à-Pitre University Hospital from May to September 2014. We collected data prospectively from infants hospitalized for Chikungunya disease. RESULTS: A total of 154 infants were included. Hyperthermia was greater than 38.5°C the first 48h and during on average 2.7 days. Pain (on mobilization and/or cutaneous hyperesthesia and/or arthralgia) was present in 82% of the cases. Loss of appetite was reported for 62% of the infants. Initial maculopapular erythematous eruption occurred in 69% of the cases. A vesiculobullous eruption was secondarily observed in 7% of the cases. Edema on the feet and/or hands was present in 48% of the cases. Febrile seizure was observed in 12% of the cases. Lymphopenia was the most frequent laboratory finding, present in 94% of the infants. No cases of thrombocytopenia were observed. The reported complications were: bullous epidermolysis, state of epilepticus, and severe acute hepatitis. CONCLUSION: This study highlights a suggestive clinical presentation of Chikungunya diseases combining pain, fever, tachycardia, foot and/or hand edema. Lymphopenia, monocytosis, and the absence of thrombocytopenia were relevant biological signs.

[Cardiac rehabilitation in adults with congenital heart diseases]. / Réadaptation cardiaque des adultes avec cardiopathies congénitales.

The great advances in the medical and surgical management of congenital heart diseases have allowed many children to reach adulthood with often a good hemodynamic result. Nevertheless most of these adults have a limitation of their functional capacity. This limitation is more or less important, penalizes them in their daily life and alters their quality of life. The origin of this limitation is generally multifactorial. It is linked, of course, to the severity of the heart disease and the quality of the operative result. But there is very often a physical deconditioning. It can be secondary to the heart disease but is often secondary to a lack of physical activity. It is the parents, sometimes overprotective, but frequently the doctors who imposed, often wrongly, this restriction. It is essential to take this dimension into account in view of the important benefits expected for health and quality of life. Cardiac rehabilitation is a privileged tool for providing advice in a suitable environment. This requires close collaboration between cardiac rehabilitators and congenital cardiologists to offer appropriate care. We bring here some reflections and the basic elements to guide the re-training of these patients.

Correlation between cardio-pulmonary exercise test variables and health-related quality of life among children with congenital heart diseases.

BACKGROUND: Health-related quality of life (HR-QoL) stands as a determinant "patient-related outcome" and correlates with cardio-pulmonary exercise test (CPET) in adults with chronic heart failure or with a congenital heart disease (CHD). No such correlation has been established in pediatric cardiology. METHODS AND RESULTS: 202 CHD children aged 8 to 18 performed a CPET (treadmill n=96, cycle-ergometer n=106). CHD severity was stratified into 4 groups. All children and parents filled out the Kidscreen HR-QoL questionnaire. Peak VO2, anaerobic threshold (AT), and oxygen pulse followed a downward significant trend with increasing CHD severity and conversely for VE/VCO2 slope. Self-reported and parent-reported physical well-being HR-QoL scores correlated with peak VO2 (respectively r=0.27, p<0.0001 and r=0.43, p<0.0001), percentage of predicted peak VO2 (r=0.28, p=0.0001 and r=0.41, p<0.0001), and percentage of predicted VO2 at AT (r=0.22, p<0.01 and r=0.31, p<0.0001). Significant correlations were also observed between several HR-QoL dimensions and dead space to tidal volume ratio (VD/VT), oxygen uptake efficiency slope (OUES), oxygen pulse but never with VE/VCO2 slope. The strongest correlations were observed in the treadmill group, especially between peak VO2 and physical well-being for parents (r=0.57, p<0.0001) and self (r=0.40, p<0.0001) reported HR-QoL. CONCLUSIONS: Peak VO2 and AT are the two CPET variables that best correlated with HR-QoL in this large pediatric cohort, parents' reports being more accurate. If HR-QoL is involved as a "PRO" in a pediatric cardiology clinical trial, we suggest using parents related physical well-being HR-QoL scores. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (number NCT01202916).

Quality of Life of Children with Congenital Heart Diseases: A Multicenter Controlled Cross-Sectional Study.

To assess the health-related quality of life (QoL) in children with congenital heart diseases (CHD) with a validated questionnaire in comparison with control children. We prospectively recruited 282 children with CHD aged from 8 to 18 years in two tertiary care centers (France and Belgium) and 180 same-age controls in randomly selected French schools. Children's QoL was self-reported with the KIDSCREEN-52 questionnaire and reported by parents with the KIDSCREEN-27. QoL scores of each dimension were compared between CHD and controls and between the classes of disease severity. Both centers were comparable for most demographic and clinical data. Age- and gender-adjusted self-reported QoL scores were lower in CHD children than in controls for physical well-being (mean ± SEM 45.97 ± 0.57 vs 50.16 ± 0.71, p < 0.0001), financial resources (45.72 ± 0.70 vs 48.85 ± 0.87, p = 0.01), peers/social support (48.01 ± 0.72 vs 51.02 ± 0.88, p = 0.01), and autonomy in the multivariate analysis (47.63 ± 0.69 vs 49.28 ± 0.85, p = 0.04). Parents-reported scores were lower in CHD children for physical (p < 0.0001), psychological well-being (p = 0.04), peers/social support (p < 0.0001), and school environment (p < 0.0001) dimensions. Similarly, the disease severity had an impact on physical well-being (p < 0.001), financial resources (p = 0.05), and peers/social support (p = 0.01) for self-reported dimensions, and on physical well-being (p < 0.001), psychological well-being (p < 0.01), peers/social support (p < 0.001), and school environment (p < 0.001) for parents-reported dimensions. However, in multivariate analysis on self-reported QoL, disease severity was significantly associated with the self-perception dimension only. Self-reported QoL of CHD children was similar to that of same-age healthy children in seven of 10 dimensions, but parents-reported QoL was impaired in four of five dimensions.

[A monocenter experience of ventricular septal defects treated by catherization]. / Expérience monocentrique de la fermeture par cathétérisme interventionnel des communications interventriculaires.

INTRODUCTION: Studies on ventricular septal defects closure by catheterization confirm its feasibility without reporting clearly the indications and difficulties encountered. PATIENTS AND RESULTS: From 2001 to end-2006, 22 patients benefited from 26 ventricular septal defects closure (15 muscular and 7 membranous) at a median age and weight of 2.1 years and 12.5 kg, respectively. A perventricular catheterization was performed in 2 cases. Eighteen patients (82%) benefited from 21 prostheses with success. The closure was associated to surgery in 9 cases (41%) whereas it substituted surgery in the other 13 cases (59%). The median duration of the procedure was significantly longer in case of muscular ventricular septal defects (215 min (175-510) vs. 170 min (120-225), p=0.04). Major complications are reported in 5 cases out of 26 catheterization (19%), including one death related to conduction block, occurring after the implantation of two prostheses in a patient with aortopulmonary transposition. All other associated cardiac diseases have been corrected. A prosthetic emboli occurred in one case, 1.5 months after implantation. It had been retrieved by catheterization. Two patients died afterwards from non-procedure-related causes. After a median follow-up of 1.1 years, the 17 other patients remained asymptomatic. One child with a perimembranous prosthesis presents a paroxystic atrio-ventricular block. CONCLUSION: Even though indispensable for the curative treatment of several congenital cardiac diseases including non-operable ventricular septal defects, this procedure is related to a substantial rate of mortality and morbidity. The risk of atrio-ventricular block must be adequately considered in case of membranous ventricular septal defects.

[Long-term results of complete atrio-ventricular canal correction]. / Résultats à long terme du traitement chirurgical du canal atrioventriculaire complet.

OBJECTIVES: To assess the prognosis of surgically corrected complete atrio-ventricular canal and determine risk factors for death and redo surgery. PATIENTS: and method: From January 1984 to March 2006, 126 patients were distributed in 3 groups according to their date of intervention: group I (1984-1991), group II (1992-1999) and group III (2000-2006). They were operated at mean age of 8.35 + 13.3 months. Down syndrome was present in 99 patients (79%). A partial or total closure of the left atrio-ventricular valvular cleft was performed in 47 patients (37%). RESULTS: The in-hospital mortality was at 14.28% (18 patients), including 23.7% in group I, 16.2% in group II and 4.4% in group III (p=0.06). The predictive factors of survival were the Down syndrome (p<0.05) and surgery of the left atrio-ventricular valvular cleft (p=0.05). An early reoperation was required in 6 cases, for a severe leak of this valve (n=4) or an important residual shunt (n=2). After a mean follow-up of 9.5+6.9 years, the survival rate was at 83.6% and 10 patients (9.9%) had a redo surgery for a leak of the left atrio-ventricular valve (n=6) or sub-aortic stenosis (n=4). The rate of no-redo surgery for valve insufficiency was at 94.2% at 5 years, 91.1% at 10 years and 87.6% at 15 years. CONCLUSION: The surgical treatment of complete atrio-ventricular canal became more and more efficient with poor rates of mortality and redo surgery during these last years. The closure of the left atrio-ventricular valve cleft, mostly partial, is frequently performed. Patients with the Down syndrome have a better vital prognosis and lower rates of long-term redo surgery.

[Rehabilitation of hypoplastic pulmonary arteries in pulmonary atresia with ventricular septal defect. Medium term results]. / Réhabilitation des artères pulmonaires hypoplasiques dans l'atrésie pulmonaire avec communication interventriculaire. Résultats à moyen terme.

The treatment of pulmonary atresia with ventricular septal defect, hypoplasia of the native pulmonary arteries and major aorto-pulmonary collaterals is controversial with a wide range of options from symptomatic treatment to surgical correction, but usually unifocal surgery. However, the collateral vessels used in the reconstruction are often tortuous and stenosed, resulting in a problematic haemodynamic result. The authors report the results of medico-surgical rehabilitation of the native pulmonary arteries in three stages. Since 1990, patients with an average Nakata index of 27.5 +/- 16.7 mm2/m2 underwent elective surgical connection of the native pulmonary arteries to the right ventricle (1st stage) followed by their rehabilitation with catheter occlusion of the collaterals (2nd stage) with the aim of preparing surgical correction (3rd stage). The first surgical stage at an median age of 5 months (0.1 to 25.2) was complicated by one death. After an average of 2.1 +/- 1 catheterisations, 17 patients underwent surgical correction at an median age of 2.18 (0.6 to 10.3) years with an average Nakata index of 207 +/- 91 mm2/m2. All survived surgery with three late deaths in patients with poor haemodynamic results (right ventricular/left ventricular pressure ratio>80%). After an median follow-up of 9.2 (3.5 to 17) years, the 14 survivors are in NYHA Class I or II with a good haemodynamic result in 10 patients. The authors conclude that despite some late deaths and raised right ventricular and pulmonary artery pressures in a minority of patients, the rehabilitation of the pulmonary arteries is an effective management of this cardiopathy.

Inherited long QT syndrome revealed by antifungals drug-drug interaction.

A 14-year-old Tahitian girl with acute myeloid leukaemia and a suspected mucormucosis infection was treated with intravenous voriconazole and caspofungin. Because of worsening of fungal infection, voriconazole was switched to posaconazole. During the switch, the patient presented with QT interval prolongation with 'torsades de pointes' and reversible cardiac arrest. Voriconazole plasma level measured 15 h after the last administration was 7 mg/L. Genotyping suggested that the patient was an extensive metabolizer with respect to CYP2C9 and CYP2C19. The association of antifungal agents with pro-arrhythmogenic drugs and other risk factors led to torsades de pointes and the revealing of inherited QT syndrome.