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.

Sudden death by arrythmia in a 4-year-old boy.

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 12min 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.

[The myth of virgin cleansing: Latest news on an archaic magico-religious practice]. / Le mythe du nettoyage par les vierges : actualité d'un archaïsme magico-religieux.

BACKGROUND: In the medical anthropology section of the Nanterre Hospital (France) for migrants and refugees, three cases were recorded of "virgin cleansing" in sub-Saharan African countries. PATIENTS AND METHODS: These consisted of sexual assaults (2 instances of rape and 1 of sexual interference) on sexually immature females (young girls) by patients with sexually transmitted infections (mainly HIV, syphilis) hoping they might thereby be cured. DISCUSSION: These particularly atrocious hetero-aggressive sexual practices based on magical arguments are unfortunately universal and are not limited to a specific culture. At the medical anthropology level, the belief in cleansing by virgins is based on the notion that the patient is dirty and impure. In the same way that emetics and/or laxatives are prescribed in the case of intestinal disorders (to "eliminate" the disease), some subjects use diuretics for urinary abnormalities or, literally, "clean vaginas (or anuses)" to purge their own miasma. The rising tide of population migrations (some of whom carry chronic infections), refugee camps, prolonged incarcerations, etc., makes observations of such phenomena increasingly frequent. Belief in cleansing by virgins (and the fatal consequences thereof) will be difficult to eradicate. The education of populations and health professionals should promote absolute respect for the body of children, and, more generally, of others, particularly since at this time of increasingly marked migratory flows, this problem sadly risks becoming widespread.

[Severe nutritional rickets in young children: Resurgence of an old disease]. / Rachitisme carentiel sévère du nourrisson : de nouveau d'actualité.

Nutritional rickets remains a significant public health issue for children worldwide. Although it has almost disappeared in industrialized countries following routine vitamin D supplementation, recent evidence suggests an increasing incidence, especially in young children. In addition to the classical clinical consequences on bone and the growth plate, rickets may also be associated with life-threatening neurological and cardiac complications in the most severe forms. Consequently, early screening and treatment are required. Here, we report the case of a 2-year-old child who presented with severe nutritional rickets associated with seizure and cardiomyopathy. Family screening revealed rickets in all the siblings. This case report emphasizes the importance of being aware of this disease, notably in population with sociocultural risk factors.

["Palimpsest scar" lesions in a context of torture (Darfur, Sudan)]. / Cicatrices « palimpsestes ¼ en contexte de torture (Darfour, Soudan).

BACKGROUND: As a result of the current exponentially growing refugee population from the Middle-East and East Africa (Sudan, Darfur, Eritrea), clinicians (including forensic pathologists) are seeing atypical skin lesions, mainly of a traumatic nature, but in some cases associated with long-standing lesions related to ethnic practices. PATIENTS AND METHODS: A case of torture sequelae is presented herein in a patient originally from Darfur (Sudan): cutaneous incisions were made on old scars several times using a knife. DISCUSSION: The clinical presentation of scarification lesions and that of atypically healed wounds (presumably an effect of inflammation induced by the introduction of irritating foreign bodies such as sand, salt, etc.) are completely different: in all cases they indicate a relative timeframe of the facts, which the clinician should not overlook in reconstructing the patient's course and the injuries to which he has been subjected (hence the proposed designation of "palimpsest scar", in the sense that a palimpsest is a manuscript on a parchment that previously contained writing but has been scratched clean to be overwritten). Thus, a "palimpsest scar" constitutes a fresh scar on top of and hiding another (ritual) scar in a context of ethnic cleansing. The diagnostic and clinical significance comes from the importance of differentiating between ethnic-type lesions and those induced by physical violence and abuse in a context of war.

[Loeys-Dietz syndrome (TGFßR2 mutation) in a 4-year-old child with thoracic aortic aneurysm]. / Syndrome de Loeys-Dietz (mutation TGFßR2) chez une enfant de 4ans avec anévrysme de l'aorte thoracique.

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 TGFßR2 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-ß vasculopathy such as Loeys-Dietz syndrome.

[Embolization of pulmonary arteriovenous malformation causing hypoxemia in a 7-year-old child]. / Fermeture percutanée d'une fistule artério-veineuse pulmonaire responsable d'une hypoxémie chronique chez une enfant de 7 ans.

Pulmonary arteriovenous fistulas are abnormal vessels joining the right pulmonary artery to the pulmonary veins. They lead to an extracardiac right-to-left shunt with refractory hypoxemia. We report the case of a 7-year-old girl with a large pulmonary arteriovenous fistula discovered with refractory hypoxemia diagnosed during general anesthesia for adenoidectomy. Radio-opacity was observed on the upper lobe of the right lung. The diagnosis was made using thoracic angiotomography. The proximal arterial vessel arose from the lobar pulmonary artery. The fistula had developed in the entire right upper lobe and drained into two veins flowing into the right superior pulmonary artery. Given the marked hypoxemia, the potential risks of pulmonary hemorrhage and pulmonary infection, an occlusion of the fistula was indicated. After discussion between surgeons and interventional cardiologists, catheterization was indicated. The occlusion of the fistula was successful at the second attempt after release of a vascular plug in the main proximal vessel. This case illustrates the clinical circumstances of diagnosis of arteriovenous fistula, the diagnostic algorithm for refractory hypoxemia and the therapeutic options, with discussion of the benefits and drawbacks of a catheterization procedure.

[Thiamine deficiency in infants: a case report]. / Béribéri du nourrisson : à propos d'un cas.

Thiamine deficiency is recognized in varied parts of the world. In Asia, it remains an important public health problem where highly polished rice is the major staple food and where other primary dietary sources of thiamine are in short supply. Beriberi, or clinically apparent thiamine deficiency, may present a variety of syndromes including myocardial dysfunction or wet beriberi, dry beriberi with neurological symptoms, and the more severe form Shoshin beriberi with cardiac failure and lactic acidosis. Infantile thiamine deficiency is a very rare condition in developed countries today. It occurs mainly in breastfed infants of mothers who have inadequate intake of thiamine. Clinical symptoms in such infants include gastrointestinal symptoms, cardiac failure, and lactic acidosis. We report the case of a 10-week-old girl, admitted with diarrhea, vomiting, acidosis, and cardiac failure. After excluding other etiologies of cardiomyopathy, biochemical thiamine deficiency confirmed the diagnosis of beriberi in an infant of a thiamine-deficient mother from Reunion Island, a French island where recently, with Mayotte Island, epidemic cases of beriberi have been described. This case is important to highlight the manifestations in young infants and to alert physicians to the possibility of thiamine deficiency in developed countries.

Systematic molecular and cytogenetic screening of 100 patients with marfanoid syndromes and intellectual disability.

The association of marfanoid habitus (MH) and intellectual disability (ID) has been reported in the literature, with overlapping presentations and genetic heterogeneity. A hundred patients (71 males and 29 females) with a MH and ID were recruited. Custom-designed 244K array-CGH (Agilent®; Agilent Technologies Inc., Santa Clara, CA) and MED12, ZDHHC9, UPF3B, FBN1, TGFBR1 and TGFBR2 sequencing analyses were performed. Eighty patients could be classified as isolated MH and ID: 12 chromosomal imbalances, 1 FBN1 mutation and 1 possibly pathogenic MED12 mutation were found (17%). Twenty patients could be classified as ID with other extra-skeletal features of the Marfan syndrome (MFS) spectrum: 4 pathogenic FBN1 mutations and 4 chromosomal imbalances were found (2 patients with both FBN1 mutation and chromosomal rearrangement) (29%). These results suggest either that there are more loci with genes yet to be discovered or that MH can also be a relatively non-specific feature of patients with ID. The search for aortic complications is mandatory even if MH is associated with ID since FBN1 mutations or rearrangements were found in some patients. The excess of males is in favour of the involvement of other X-linked genes. Although it was impossible to make a diagnosis in 80% of patients, these results will improve genetic counselling in families.

What do French patients and geneticists think about prenatal and preimplantation diagnoses in Marfan syndrome?

OBJECTIVES: Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with manifestations mainly involving the skeletal, ocular, and cardiovascular systems. The phenotypic variability observed in MFS makes genetic counselling difficult. Prenatal diagnosis (PND) and preimplantation genetic diagnosis are technically feasible when a causal mutation is identified, but both raise many ethical questions in this condition. Little is known about opinions and practices in such reproductive issues in MFS. The goal of this study was to report on patients' points of view and geneticists' standard practices. METHODS: Two different questionnaires were produced. RESULTS: Fifty geneticists filled in the questionnaire. Twenty-two per cent thought that PND was acceptable, 72% debatable and 6% not acceptable. Preimplantation genetic diagnosis was more often reported acceptable (34% of answers). Results varied according to the physician's experience with the disease. Fifty-four answers were collected for patients' questionnaires. Most of them (74%) were favourable to the development of prenatal testing, and believed that the choice should be given to parents. However, only a minority would opt for prenatal diagnosis for themselves. CONCLUSION: This study showed that the majority of patients were in favour of PND and that opinions among practitioners varied widely, but that overall, practitioners favoured a systematic multidisciplinary evaluation of the couple's request.

Endothelial function and mechanical arterial properties in children born small for gestational age: comparison with obese children.

BACKGROUND: Early cardiovascular events preceding atherosclerosis have been reported in children born small for gestational age (SGA). AIMS: To describe in detail the mechanical and functional arterial properties of SGA children and to compare the data to those of obese children in order to gain a better understanding of the severity of the dysfunction. A control group was required to overcome the lack of normal values. METHODS: Three groups of 7- to 15-year-old children were included. Sixty children born SGA without obesity, 49 children with obesity and not SGA, and 55 controls underwent complete carotid and brachial arterial measurements using ultrasound and flow-mediated dilation. Biological measurements were performed in the obese and SGA groups. RESULTS: Mean blood pressure and intima-media thickness were lower in SGA children than in the obese group (p < 0.001 and p = 0.004, respectively), but not different from the control group. Flow-mediated dilation was lower in SGA than in obese children and in controls (p < 0.001). CONCLUSION: These data show that children born SGA have endothelial dysfunction with normal intima-media thickness.

[Maternal group B streptococcal bacteriuria and neonatal infective endocarditis: a case report]. / Bactériurie maternelle à streptocoque B et endocardite néonatale : à propos d'un cas.

Bacterial endocarditis is rare in children. We report the case of streptococcal B endocarditis in a newborn whose mother had asymptomatic bacteriuria during pregnancy. This report emphasizes the importance of maternal intrapartum antibiotic therapy when there is a major risk of neonatal infection and underlines the diagnostic value of echocardiography in case of prolonged fever.

[Morgagni hernia causing cardiac tamponade]. / Tamponnade néonatale par hernie de Morgagni.

Morgagni hernia is a rare malformation (3% of diaphragmatic hernias). This hernia is usually asymptomatic in children. We report on a case revealed by an unusual complication. Severe cyanosis was due to right-to-left atrial shunt through the foramen ovale assessed by 2D echocardiography. Diagnosis of the Morgagni hernia was made with CT scan. The intrathoracic liver compressed the right chambers of the heart causing tamponade. Cardiac compression was reversed after surgery and replacement of the liver in the abdomen. Six months after the surgery, the infant was symptom-free with normal size right chambers of the heart.

[Fetal myocarditis associated with maternal anti-Ro and anti-La antibodies in the absence of atrioventricular block with good outcome]. / Myocardite fœtale sans trouble conductif chez une femme lupique avec anticorps anti-SSA/Ro et anti-SSB/La d'évolution favorable.

We report a case of fetal myocarditis without conductive abnormality in a pregnant woman with anti-Ro/La antibodies. Fetal echocardiography showed myocarditis with ventricular and valvular hyperechogenicity, which was confirmed by postnatal transthoracic echography. Treatment with dexamethasone (4 mg/day) was started in the 22nd week of gestation. The outcome was good, with the child remaining asymptomatic 2 years later. This observation describes one of the rare forms of fetal myocarditis with favorable outcome.

[Candida albicans endocarditis after pulmonary artery banding]. / Endocardite àCandida albicans sur cerclage de l'artère pulmonaire.

Endocarditis is uncommon in infants and is exceptionally related to Candida albicans on pulmonary banding. We report on a case in a 7-month-old infant who had pulmonary artery banding for a ventricular septal defect and who presented with candidal endocarditis. Banding was chosen because of the patient's poor trophic and unstable status, which could be risky for surgery involving extracorporeal circulation. A few weeks after the banding, the patient developed systemic Candida infection, which was treated successfully. At 7 months, cardiac failure appeared without fever or inflammatory signs. Cardiac echography showed that the banding was not protective as well as a hyperechogenic image on the pulmonary bifurcation. The angioscan showed a hypodense thrombus. Emergency surgery was performed consisting of pulmonary artery exploration, thrombectomy, and ventricular septal defect closure. The exploration showed a pulmonary artery perforation caused by the infected pseudoaneurysm and the migration of the banding into the pulmonary artery. The anatomopathologic analysis of the vegetation identified multisensitive Candida albicans. After surgery and prolonged antifungal treatment, progression was satisfactory.

Videoconference pediatric and congenital cardiology consultations: a new application in telemedicine.

BACKGROUND: The relative rarity of congenital heart disease gives it an orphean disease status, requiring specialised centres. The present maturity of information technology allows telemedicine to be integrated into current medical practice. We report our experience of telemedicine between the cardiology department at St Pierre Hospital on the island of Réunion and the pediatric cardiology department at the teaching hospital in Toulouse. AIMS: The aims of this work were to 1. verify the technical feasibility of transmitting echocardiographic images, 2. determine an optimal therapeutic strategy for each patient, and 3. deliver precise information live to patients and their families. METHODS: Five pediatric cardiology videoconference consultation sessions were transmitted between April 2006 and May 2007. The videoconference equipment, POLYCOM VSX 7000 (R), was used to relay information between the two centres, using six high-debit digital telephone lines, allowing a transfer rate of 384 kbits/s and an image frequency of 25 frames per second. The echocardiographic equipment at St Pierre Hospital was connected to the videoconference equipment by an S-VHS video output. The transmitted sources alternated between the echographic video output and the signal from a video camera, with continuous audio transmission. RESULTS: The telemedicine meeting was made up of three main elements: 1. a consultation with real-time echocardiographic acquisition and transmission, 2. a discussion between medical colleagues, and 3. a discussion with the family. Five videoconference consultation sessions were organised between April 2006 and May 2007. 22 patients were involved (median age 3 years, age range 7 days to 48 years). Heart disease was congenital in 20 patients, and acquired in 2 patients. The aim of the telemedicine consultation was to specify: 1. medical treatment in 7 patients, and 2. an indication for surgery or interventional catheterisation in 15 patients. There was no significant change in diagnosis, but in 2 patients with complex heart disease some anatomical clarifications were made. For 3 patients, the videoconference discussion was essential to get the extremely reticent families to accept the indication for surgery. CONCLUSION: This is the first experience in France of telemedicine consultation for pediatric and congenital cardiology. These videoconferences allowed patients in the south of Réunion to benefit from a specialist opinion on optimal therapeutic strategy, with no delay or need to travel a long distance.

[Evaluation of left ventricular diastolic function in children by doppler tissue imaging]. / Evaluation de la fonction diastolique par Doppler tissulaire chez l'enfant.

Left ventricular diastolic function may change at an early stage in cardiac disease. It is often difficult to assess in daily practice. The use of Doppler tissue imaging at the annulus has been validated in adults. This method is little used in paediatrics and the physiological norms have not been established in children. Forty three children aged 7 days to 241 months were referred for a cardiological opinion with normal echocardiogrammes were included. Myocardial velocities were measured by Doppler tissue imaging of the left and right ventricular walls at different moments of the cardiac cycle in the apical 4-chamber view. A complete study was possible in 39 cases (91%). Doppler tissue imaging was not performed in one case and was incomplete on the right ventricle in 3 children. The median of the lateral mitral tissue E wave (Ea) was 16.3 cm/s and that of the right ventricle was 15.8 cm/s with a tissue Ea/Aa ratio of 2.6 and 1.6 respectively. The median of the tissue S waves was 8.8 cm/s for the left ventricular lateral wall and 13.3 cm/s for the right ventricular lateral wall. The E/Ea ratio of the left ventricular lateral wall was 5.9. Although the velocities of the left ventricular lateral wall were not related to the children's' age or size, the correlations between the E/Ea ratio and age and size were statistically significant. The myocardial velocities of the neonate were characteristic and different to those of the older paediatric population (slower Ea and S waves, faster Aa with a higher E/Ea ratio). The authors conclude that Doppler tissue imaging is feasible in clinical paediatric cardiology. Comparative studies with populations with cardiac disease are necessary to determine pathological values.

[Alveolar capillary dysplasia and persistent pulmonary hypertension of the newborn]. / La dysplasie alvéolo-capillaire: une cause exceptionnelle d'hypertension artérielle pulmonaire persistante du nouveau né. A propos d'un cas.

Alveolar capillary dysplasia is a rare cause of persistent pulmonary hypertension of the newborn. The diagnosis of this condition is made by histological study of a pulmonary biopsy. Familial forms and associated genitor-urinary and gastrointestinal malformations have been reported. Despite optimal management, the prognosis remains poor. The authors report the case of a neonate who developed cyanosis and cardiogenic shock on the 10th day of life. There was no associated neonatal pathology. Echocardiography showed supra-systemic pulmonary hypertension with normal cardiac structure. Pulmonary vasodilator therapies (inhaled NO, prostacyclin, sildenafil, bosentan) were ineffective and the child died on the 25th day of life. Autopsy revealed alveolar capillary dysplasia.