Spontaneous resolution of an intrapericardial thrombus as a complication of pericardiocentesis in a neonate.

We present the case of a premature neonate with pericardial effusion secondary to extravasation of total parenteral nutrition from a mispositioned/migrated umbilical venous catheter. Emergency pericardiocentesis was complicated by an intrapericardial thrombus, which was managed conservatively with spontaneous resolution within 24 hours. This case illustrates that the rare complication of an intrapericardial thrombus after pericardiocentesis can be successfully managed conservatively with close monitoring in haemodynamically stable paediatric patients.

Evaluation of late cardiac effects after multisystem inflammatory syndrome in children.

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is associated with important cardiovascular morbidity during the acute phase. Follow-up shows a swift recovery of cardiac abnormalities in most patients. However, a small portion of patients has persistent cardiac sequelae at mid-term. The goal of our study was to assess late cardiac outcomes of MIS-C. Methods: A prospective observational multicenter study was performed in children admitted with MIS-C and cardiac involvement between April 2020 and March 2022. A follow-up by NT-proBNP measurement, echocardiography, 24-h Holter monitoring, and cardiac MRI (CMR) was performed at least 6 months after MIS-C diagnosis. Results: We included 36 children with a median age of 10 (8.0-11.0) years, and among them, 21 (58%) were girls. At diagnosis, all patients had an elevated NT-proBNP, and 39% had a decreased left ventricular ejection fraction (LVEF) (<55%). ECG abnormalities were present in 13 (36%) patients, but none presented with arrhythmia. Almost two-thirds of patients (58%) had echocardiographic abnormalities such as coronary artery dilation (20%), pericardial effusion (17%), and mitral valve insufficiency (14%). A decreased echocardiographic systolic left ventricular (LV) function was detected in 14 (39%) patients. A follow-up visit was done at a mean time of 12.1 (±5.8) months (range 6-28 months). The ECG normalized in all except one, and no arrhythmias were detected on 24-h Holter monitoring. None had persistent coronary artery dilation or pericardial effusion. The NT-proBNP level and echocardiographic systolic LV function normalized in all patients, except for one, who had a severely reduced EF. The LV global longitudinal strain (GLS), as a marker of subclinical myocardial dysfunction, decreased (z < -2) in 35%. CMR identified one patient with severely reduced EF and extensive myocardial fibrosis requiring heart transplantation. None of the other patients had signs of myocardial scarring on CMR. Conclusion: Late cardiac outcomes after MIS-C, if treated according to the current guidelines, are excellent. CMR does not show any myocardial scarring in children with normal systolic LV function. However, a subgroup had a decreased GLS at follow-up, possibly as a reflection of persistent subclinical myocardial dysfunction.

A Severe Form of Familial Desminopathy Due to a Homozygous Nonsense DES Variant in Two Siblings.

Familial primary desminopathies are usually autosomal dominantly inherited and present at the age of 20 to 40 years with progressive muscle weakness and atrophy, cardiomyopathy, and cardiac arrhythmias. Cardiac features may precede the muscular weakness. Here, we report the rare case of two siblings presenting with a desminopathy at pediatric age, due to homozygous nonsense variations (c.700G > T [p.Glu234Ter]) in DES, representing an autosomal recessive inheritance pattern. The homozygous state of these variants is expected to result in the complete absence of desmin production. Rare autosomal recessive DES variants are associated with an earlier clinical presentation (from childhood to early adulthood) and faster evolution compared with more common autosomal dominant variants. A normal resting electrocardiography (ECG) and cardiac ultrasound can be a pitfall, as seen in our patient who has extensive fibrotic scarring on cardiac magnetic resonance imaging (MRI). We recommend yearly cardiac ultrasound, yearly 24-hour Holter monitoring and 2 yearly cardiac MRI from the age of 10 years in all asymptomatic patients. Heterozygous patients usually have no or only mild complaints but, though not yet reported in autosomal recessive desminopathies, muscular complaints are possible, as seen in the father of our patients. The prognosis for these patients with desminopathy presenting in childhood is unpredictable but anticipated as poor.

Blood transcriptomics to facilitate diagnosis and stratification in pediatric rheumatic diseases - a proof of concept study.

BACKGROUND: Transcriptome profiling of blood cells is an efficient tool to study the gene expression signatures of rheumatic diseases. This study aims to improve the early diagnosis of pediatric rheumatic diseases by investigating patients' blood gene expression and applying machine learning on the transcriptome data to develop predictive models. METHODS: RNA sequencing was performed on whole blood collected from children with rheumatic diseases. Random Forest classification models were developed based on the transcriptome data of 48 rheumatic patients, 46 children with viral infection, and 35 controls to classify different disease groups. The performance of these classifiers was evaluated by leave-one-out cross-validation. Analyses of differentially expressed genes (DEG), gene ontology (GO), and interferon-stimulated gene (ISG) score were also conducted. RESULTS: Our first classifier could differentiate pediatric rheumatic patients from controls and infection cases with high area-under-the-curve (AUC) values (AUC = 0.8 ± 0.1 and 0.7 ± 0.1, respectively). Three other classifiers could distinguish chronic recurrent multifocal osteomyelitis (CRMO), juvenile idiopathic arthritis (JIA), and interferonopathies (IFN) from control and infection cases with AUC ≥ 0.8. DEG and GO analyses reveal that the pathophysiology of CRMO, IFN, and JIA involves innate immune responses including myeloid leukocyte and granulocyte activation, neutrophil activation and degranulation. IFN is specifically mediated by antibacterial and antifungal defense responses, CRMO by cellular response to cytokine, and JIA by cellular response to chemical stimulus. IFN patients particularly had the highest mean ISG score among all disease groups. CONCLUSION: Our data show that blood transcriptomics combined with machine learning is a promising diagnostic tool for pediatric rheumatic diseases and may assist physicians in making data-driven and patient-specific decisions in clinical practice.

Pharmacological cardioversion of supraventricular tachycardia in pregnancy during continuous electrophysiological foetal monitoring: a case report.

Background: Maternal tachycardia is the most frequently occurring cardiac complication during pregnancy. Often administration of drugs is required as a treatment. The drug of choice is intravenously administered adenosine because it is considered safe, though there are limited studies regarding safety for the foetus with the use of adenosine. Case summary: We report a conversion of maternal atrio-ventricular (AV) nodal reentry tachycardia during pregnancy with the use of intravenous adenosine whilst continuous electrophysiological foetal monitoring. Four seconds after the maternal conversion, the foetal tracing suggests the presence of a ventricular extrasystole or a transient AV block. Discussion: This case report illustrates that the administration of adenosine intravenously during pregnancy could have an effect on the foetal conduction system. Therefore, further investigation to assess the electrophysiological effect of adenosine on the foetal electrocardiogram seems required.

Therapeutic drug monitoring of fenfluramine in clinical practice: Pharmacokinetic variability and impact of concomitant antiseizure medications.

OBJECTIVE: This study was undertaken to determine the plasma concentration and pharmacokinetic variability of fenfluramine (FFA) and its main active metabolite norfenfluramine (norFFA) in relation to the prevalence of adverse effects in patients with refractory epilepsy treated with FFA. In addition, the interaction with concomitant antiseizure medications including stiripentol (STP) is studied. METHODS: Patients were recruited at our center from two open-label sources, an investigator-initiated observational study and an international multicenter extension study. Venous blood samples were collected between June 2015 and December 2020. Plasma FFA and norFFA concentrations were determined by liquid chromatography tandem spectrometric analysis. Clinical data were collected retrospectively. Intrapatient coefficient of variation was calculated for all patients with at least three samples. Interpatient variability was calculated based on the concentration to weight-adjusted dose ratio (C/D) of all patients. RESULTS: We collected 321 samples from 61 patients (49 with Dravet syndrome, seven with Lennox-Gastaut syndrome, and five with a developmental and epileptic encephalopathy). With a mean daily dose of .33 mg/kg/day (SD = ±.16), the median FFA plasma concentration was 41.4 µg/L (range = 5.1-712.5) and median norFFA concentration 28.1 µg/L (range = 2.6-149.6). The FFA plasma concentration was linearly related to the daily dose (p < .001) and norFFA levels (p < .001). The C/D of FFA increased with age (p < .001). Median FFA C/D was 428% higher (p < .001), norFFA C/D 83% lower (p < .001), and norFFA/FFA 23% lower (p < .001) in patients treated with STP comedication. Higher FFA concentration was associated with fatigue (p = .001) and somnolence (p < .001), but not anorexia (p = .0619) or reduction in seizure frequency (p = .772). Gender and other ASMs were not associated with significant variations in (nor)FFA C/D ratio. SIGNIFICANCE: Most FFA levels are in the lower range (<50 µg/L), although a high interpatient and intrapatient variability is present. In combination with STP, the dose of FFA should be reduced.

Compound Heterozygous SCN5A Mutations in Severe Sodium Channelopathy With Brugada Syndrome: A Case Report.

Aims: Brugada syndrome (BrS) is an inherited cardiac arrhythmia with an increased risk for sudden cardiac death (SCD). About 20% of BrS cases are explained by mutations in the SCN5A gene, encoding the main cardiac sodium Nav1.5 channel. Here we present a severe case of cardiac sodium channelopathy with BrS caused by SCN5A compound heterozygous mutations. We performed a genetic analysis of SCN5A in a male proband who collapsed during cycling at the age of 2 years. Because of atrial standstill, he received a pacemaker, and at the age of 3 years, he experienced a collapse anew with left-sided brain stroke. A later ECG taken during a fever unmasked a characteristic BrS type-1 pattern. The functional effect of the detected genetic variants was investigated. Methods and Results: Next-generation sequencing allowed the detection of two SCN5A variants in trans: c.4813+3_4813+6dupGGGT-a Belgian founder mutation-and c.4711 T>C, p.Phe1571Leu. A familial segregation analysis showed the presence of the founder mutation in the proband's affected father and paternal aunt and the de novo occurrence of the p.Phe1571Leu. The functional effect of the founder mutation was previously described as a loss-of-function. We performed a functional analysis of the p.Phe571Leu variant in HEK293 cells alone or co-expressed with the ß1-subunit. Compared to the SCN5A wild type, p.Phe1571Leu displayed a hyperpolarizing shift in the voltage dependence of inactivation (loss-of-function), while the activation parameters were unaffected. Using the peptide toxin nemertide α-1, the variant's loss-of-function effect could be restored due to a toxin-dependent reduction of channel inactivation. Conclusion: This is the first report providing support for the pathogenicity of the p.Phe1571Leu SCN5A variant which, together with the c.4813+3_4813+6dupGGGT founder mutation, explains the severity of the phenotype of cardiac sodium channelopathy with BrS in the presented case.

Electrocardiographic Effects of Propofol versus Etomidate in Patients with Brugada Syndrome.

BACKGROUND: Brugada Syndrome is an inherited arrhythmogenic disease, characterized by the typical coved type ST-segment elevation in the right precordial leads from V1 through V3. The BrugadaDrugs.org Advisory Board recommends avoiding administration of propofol in patients with Brugada Syndrome. Since prospective studies are lacking, it was the purpose of this study to assess the electrocardiographic effects of propofol and etomidate on the ST- and QRS-segments. In this trial, it was hypothesized that administration of propofol or etomidate in bolus for induction of anesthesia, in patients with Brugada Syndrome, do not clinically affect the ST- and QRS-segments and do not induce arrhythmias. METHODS: In this prospective, double-blinded trial, 98 patients with established Brugada syndrome were randomized to receive propofol (2 to 3 mg/kg) or etomidate (0.2 to 0.3 mg/kg) for induction of anesthesia. The primary endpoints were the changes of the ST- and QRS-segment, and the occurrence of new arrhythmias upon induction of anesthesia. RESULTS: The analysis included 80 patients: 43 were administered propofol and 37 etomidate. None of the patients had a ST elevation greater than or equal to 0.2 mV, one in each group had a ST elevation of 0.15 mV. An ST depression up to -0.15mV was observed eleven times with propofol and five with etomidate. A QRS-prolongation of 25% upon induction was seen in one patient with propofol and three with etomidate. This trial failed to establish any evidence to suggest that changes in either group differed, with most percentiles being zero (median [25th, 75th], 0 [0, 0] vs. 0 [0, 0]). Finally, no new arrhythmias occurred perioperatively in both groups. CONCLUSIONS: In this trial, there does not appear to be a significant difference in electrocardiographic changes in patients with Brugada syndrome when propofol versus etomidate were administered for induction of anesthesia. This study did not investigate electrocardiographic changes related to propofol used as an infusion for maintenance of anesthesia, so future studies would be warranted before conclusions about safety of propofol infusions in patients with Brugada syndrome can be determined.

Obstructive teratoma in the right ventricle of a newborn: a case report.

BACKGROUND: A newborn was diagnosed by echocardiogram with an asymptomatic cardiac mass in the right ventricle after a systolic cardiac murmur was detected at birth. CASE PRESENTATION: Nine days after birth, the newborn presented with three syncopal episodes and oxygen desaturation which required resuscitation. The mass induced a complete right ventricular outflow tract obstruction. The presence of a patent foramen oval and a patent ductus arteriosus explained the absence of symptoms at birth. Surgery was rapidly considered since the situation was life threatening. The tumor was successfully resected. The mass was a mature teratoma confirmed by microscopic examination, illustrated by pictures and video. CONCLUSIONS: This case was unique because of the absence of symptoms in the first 9 days of the newborn's life even though symptoms should have mounted due to the obstruction postpartum. The delay was correlated to the closure of the patent ductus arteriosus. It is recommended that newborns with any cardiac mass be followed up regularly due to hemodynamic changes at birth.

Drug-induced brugada syndrome in children: clinical features, device-based management, and long-term follow-up.

OBJECTIVES: The goal of this study was to investigate the clinical features, management, and long-term follow-up of children with drug-induced Brugada syndrome (BS). BACKGROUND: Patients with BS <12 years of age with a spontaneous type I electrocardiogram have a higher risk of arrhythmic events. Data on drug-induced BS in patients <12 years of age are lacking. METHODS: Among 505 patients with ajmaline-induced BS, subjects ≤12 years of age at the time of diagnosis were considered as children and eligible for this study. RESULTS: Forty children (60% male; age 8 ± 2.8 years) were included. Twenty-four children (60%) had a family history of sudden death. Two (5%) had a previous episode of aborted sudden death, and 8 (20%) had syncope. Children experienced more frequent episodes of sinus node dysfunction (SND) compared with older subjects (7.5% vs. 1.5%; p = 0.04) and had a comparable incidence of atrial tachyarrhythmias. Children more frequently experienced episodes of ajmaline-induced sustained ventricular arrhythmias (VAs) compared with older patients (10.0% vs. 1.3%; p = 0.005). Twelve children (30%) received an implantable cardioverter-defibrillator (ICD). After a mean follow-up time of 83 ± 51 months, none of the children died suddenly. Spontaneous sustained VAs were documented in 1 child (2%). Among children with ICD, 1 (8%) experienced an appropriate shock, 4 (33%) had inappropriate ICD shocks, and 4 (33%) experienced device-related complications. CONCLUSIONS: Drug-induced BS is associated with atrial arrhythmias and SND. Children are at higher risk of ajmaline-induced VAs. The rate of device-related complications, leading to lead replacement or inappropriate shocks, is considerable and even higher than with appropriate interventions. Based on these findings, the optimal management of BS in childhood should remain individualized, taking into consideration the patient's clinical history and family's wishes.