Objective To assess clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2associated multisystem inflammatory syndrome in children (MIS-C). Study design Children with MIS-C admitted to pediatric intensive care units in New York City between April 23 and May 23, 2020, were included. Demographic and clinical data were collected. Results Of 33 children with MIS-C, the median age was 10 years; 61% were male; 45% were Hispanic/Latino; and 39% were black. Comorbidities were present in 45%. Fever (93%) and vomiting (69%) were the most common presenting symptoms. Depressed left ventricular ejection fraction was found in 63% of patients with median ejection fraction of 46.6% (IQR, 39.5-52.8). C-reactive protein, procalcitonin, d-dimer, and pro-B-type natriuretic peptide levels were elevated in all patients. For treatment, intravenous immunoglobulin was used in 18 (54%), corticosteroids in 17 (51%), tocilizumab in 12 (36%), remdesivir in 7 (21%), vasopressors in 17 (51%), mechanical ventilation in 5 (15%), extracorporeal membrane oxygenation in 1 (3%), and intra-aortic balloon pump in 1 (3%). The left ventricular ejection fraction normalized in 95% of those with a depressed ejection fraction. All patients were discharged home with median duration of pediatric intensive care unit stay of 4.7 days (IQR, 4-8 days) and a hospital stay of 7.8 days (IQR, 6.0-10.1 days). One patient (3%) died after withdrawal of care secondary to stroke while on extracorporeal membrane oxygenation. Conclusions Critically ill children with coronavirus disease-2019-associated MIS-C have a spectrum of severity broader than described previously but still require careful supportive intensive care. Rapid, complete clinical and myocardial recovery was almost universal.

In a high-risk pediatric HCM cohort, ICD interventions terminating life-threatening ventricular tachyarrhythmias were frequent. Extreme left ventricular hypertrophy was most frequently associated with appropriate interventions. The rate of device complications adds a measure of complexity to ICD decisions in this age group.

This review aims to describe the past history, present techniques and future directions in transcatheter treatment of patent ductus arteriosus (PDA). Transcatheter PDA closure is the standard of care in most cases and PDA closure is indicated in any patient with signs of left ventricular volume overload due to a ductus. In cases of left-to-right PDA with severe pulmonary arterial hypertension, closure may be performed under specific conditions. The management of clinically silent or very tiny PDAs remains highly controversial. Techniques have evolved and the transcatheter approach to PDA closure is now feasible and safe with current devices. Coils and the Amplatzer Duct Occluder are used most frequently for PDA closure worldwide, with a high occlusion rate and few complications. Transcatheter PDA closure in preterm or low-bodyweight infants remains a highly challenging procedure and further device and catheter design development is indicated before transcatheter closure is the treatment of choice in this delicate patient population. The evolution of transcatheter PDA closure from just 40 years ago with 18F sheaths to device delivery via a 3F sheath is remarkable and it is anticipated that further improvements will result in better safety and efficacy of transcatheter PDA closure techniques.

Abnormalities were observed at intermediate follow-up following IS placement for treatment of native and recurrent coarctation of the aorta. Not exceeding a balloon:coarctation ratio of 3.5 and avoidance of prestent angioplasty decreased the likelihood of encountering an abnormal follow-up imaging study in patients undergoing intravascular stent placement for the treatment of coarctation of the aorta. We recommend IAI for all patients undergoing IS placement for treatment of CoA.

Understanding the basis for differential responses to drug therapies remains a challenge despite advances in genetics and genomics. Induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to investigate the pharmacology of disease processes in therapeutically and genetically relevant primary cell types in vitro and to interweave clinical and basic molecular data. We report here the derivation of iPSCs from a long QT syndrome patient with complex genetics. The proband was found to have a de novo SCN5A LQT-3 mutation (F1473C) and a polymorphism (K897T) in KCNH2, the gene for LQT-2. Analysis of the biophysics and molecular pharmacology of ion channels expressed in cardiomyocytes (CMs) differentiated from these iPSCs (iPSC-CMs) demonstrates a primary LQT-3 (Na+ channel) defect responsible for the arrhythmias not influenced by the KCNH2 polymorphism. The F1473C mutation occurs in the channel inactivation gate and enhances late Na+ channel current (INaL) that is carried by channels that fail to inactivate completely and conduct increased inward current during prolonged depolarization, resulting in delayed repolarization, a prolonged QT interval, and increased risk of fatal arrhythmia. We find a very pronounced rate dependence of INaL such that increasing the pacing rate markedly reduces INaL and, in addition, increases its inhibition by the Na+ channel blocker mexiletine. These rate-dependent properties and drug interactions, unique to the proband’s iPSC-CMs, correlate with improved management of arrhythmias in the patient and provide support for this approach in developing patient-specific clinical regimens.

Moderate to large PDAs can be effectively and safely closed using the ADO device, with excellent initial and one-year results. This device should obviate the need for multiple coils or surgical intervention for these defects.

Atrioventricular block is classified as congenital if diagnosed in utero, at birth, or within the first month of life. The pathophysiological process is believed to be due to immune-mediated injury of the conduction system, which occurs as a result of transplacental passage of maternal anti-SSA/Ro-SSB/La antibodies. Childhood atrioventricular block is therefore diagnosed between the first month and the 18th year of life. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited progressive cardiac conduction disorders. Indications and techniques of cardiac pacing have also evolved to allow safe permanent cardiac pacing in almost all patients, including those with structural heart abnormalities.Conclusion: Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current understanding of the pathogenetic mechanisms, clinical course, and optimal management of congenital and childhood AV block. What is Known: • Prevalence of congenital heart block of 1 per 15,000 to 20,000 live births. AV block is defined as congenital if diagnosed in utero, at birth, or within the first month of life, whereas childhood AV block is diagnosed between the first month and the 18th year of life. As a result of several different etiologies, congenital and childhood atrioventricular block may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Cardiac pacing is indicated in symptomatic patients and has several prophylactic indications in asymptomatic patients to prevent sudden death. • Autoimmune, congenital AV block is associated with a high neonatal mortality rate and development of dilated cardiomyopathy in 5 to 30 % cases. What is New: • Several genes including SCN5A have been implicated in autosomal dominant forms of familial progressive cardiac conduction disorders. • Leadless pacemaker technology and gene therapy for biological pacing are promising research fields. In utero percutaneous pacing appears to be at high risk and needs further development before it can be adopted into routine clinical practice. Cardiac resynchronization therapy is of proven value in case of pacing-induced cardiomyopathy.

Background SCN5A encodes the α-subunit (Nav1.5) of the principle Na+ channel in the human heart. Genetic lesions in SCN5A can cause congenital long QT syndrome (LQTS) variant 3 (LQT-3) in adults by disrupting inactivation of the Nav1.5 channel. Pharmacological targeting of mutation-altered Na+ channels has proven promising in developing a gene-specific therapeutic strategy to manage specifically this LQTS variant. SCN5A mutations that cause similar channel dysfunction may also contribute to sudden infant death syndrome (SIDS) and other arrhythmias in newborns, but the prevalence, impact, and therapeutic management of SCN5A mutations may be distinct in infants compared with adults.Methods and ResultsHere, in a multidisciplinary approach, we report a de novo SCN5A mutation (F1473C) discovered in a newborn presenting with extreme QT prolongation and differential responses to the Na+ channel blockers flecainide and mexiletine. Our goal was to determine the Na+ channel phenotype caused by this severe mutation and to determine whether distinct effects of different Na+ channel blockers on mutant channel activity provide a mechanistic understanding of the distinct therapeutic responsiveness of the mutation carrier. Sequence analysis of the proband revealed the novel missense SCN5A mutation (F1473C) and a common variant in KCNH2 (K897T). Patch clamp analysis of HEK 293 cells transiently transfected with wild-type or mutant Na+ channels revealed significant changes in channel biophysics, all contributing to the proband's phenotype as predicted by in silico modeling. Furthermore, subtle differences in drug action were detected in correcting mutant channel activity that, together with both the known genetic background and age of the patient, contribute to the distinct therapeutic responses observed clinically.SignificanceThe results of our study provide further evidence of the grave vulnerability of newborns to Na+ channel defects and suggest that both genetic background and age are particularly important in developing a mutation-specific therapeutic personalized approach to manage disorders in the young.