June

The Genetic Epidemiology of Pediatric Pulmonary Arterial Hypertension. View Article Haarman MG, Kerstjens-Frederikse WS, Vissia-Kazemier TR, Breeman KTN, Timens W, Vos YJ, Roofthooft MTR, Hillege HL, Berger RMF. J Pediatr. 2020 Jun 2:S0022-3476(20)30689-2. doi: 10.1016/j.jpeds.2020.05.051. Online ahead of print. PMID: 32502478 Take Home Points: Prevalence of pulmonary arterial hypertension (PAH)-associated gene disorders and other genetic disorder was high in pediatric patients with PAH. In this study, 27% had a PAH-associated gene mutation/variant, 17% had a genetic disorder with an established association with PAH and in 23% genetic disorders without an established association with PAH were identified. Underlying genetic mutation impact survival and can be useful in risk stratification. Comment from Dr. Shaji Menon (Salt Lake City, Utah), section editor of Pediatric Cardiology Journal Watch:   This study describes the prevalence of pulmonary arterial hypertension (PAH)-associated gene mutations, and other genetic characteristics in a national cohort of children with PAH from the Dutch National registry. The study also explores genotype-phenotype associations and outcomes. Of the 70 subjects in the study 19 (27%) had a PAH-associated gene mutation/variant: BMPR2 n = 7, TBX4 n = 8, ACVRL1 n = 1, KCNK3 n = 1, and EIF2AK4 n = 2. Twelve children (17%) had a genetic disorder with an established association with PAH (including trisomy 21 and cobalamin C deficiency). In another 16 children (23%), genetic disorders without an established association with PAH were identified (including Noonan syndrome, Beal’s syndrome, and various copy number variations). Of the 70 children tested, 40 children were diagnosed with isolated PAH. Transplant-free survival, unadjusted for clinical variables, varied significantly between groups of children with different genetic disorders. Children with CbIC deficiency and children with PVOD had the worst unadjusted outcome with a median transplant-free survival of <1 year, whereas pediatric TBX4 variant carriers showed the most favorable outcome.

Multi-System Inflammatory Syndrome in Children in Association with COVID-19. View Article Simpson JM, Newburger JW. Circulation. 2020 Jun 11. doi: 10.1161/CIRCULATIONAHA.120.048726. Online ahead of print. PMID: 32525700 Take Home Points: Multisystem inflammation in children (MIS-C) is a newly recognized syndrome mimicking Kawasaki disease in some aspects of clinical presentation and clinical course temporally associated with COVID-19 infection. Multisystem inflammatory syndrome in children shares similarities with atypical Kawasaki disease, however, clinical criteria of diagnosis of Kawasaki disease was not fulfilled. Coronary dilation including giant aneurysm can happen. Markers of inflammation and cardiac involvement—including troponin I, brain natriuretic peptide, D-dimer, C-reactive protein, and interleukin 6—were all elevated. Left ventricular systolic dysfunction requiring ionotropic support is common. Additional studies are needed to determine the longer-term impact of MIS-C on myocardial function and coronary arteries. The optimal treatment for MIS-C is uncertain. Patients are often treated with immunomodulatory therapy including intravenous immunoglobulin and steroids. In more severe cases e anakinra, infliximab, or tocilizumab has been used. Comment from Dr. Shaji Menon (Salt Lake City, Utah), section editor of Pediatric Cardiology Journal Watch:  This article is an excellent commentary on the above discussed original article by Simpson and Newburger.

Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. View Article Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A, Abakka S, Auriau J, Grimaud M, Oualha M, Beghetti M, Wacker J, Ovaert C, Hascoet S, Selegny M, Malekzadeh-Milani S, Maltret A, Bosser G, Giroux N, Bonnemains L, Bordet J, Di Filippo S, Mauran P, Falcon-Eicher S, Thambo JB, Lefort B, Moceri P, Houyel L, Renolleau S, Bonnet D.Circulation. 2020 May 17. doi: 10.1161/CIRCULATIONAHA.120.048360. Online ahead of print.PMID: 32418446 Take Home Points: Multisystem inflammatory syndrome in children (MIS-C) is a new syndrome that is temporally associated with exposure to COVID-19. Multisystem inflammatory syndrome in children shares similarities with atypical Kawasaki disease, but many clinical signs are unique. MIS-C is characterized by patients with recent diagnosis of COVID-19 presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (≥2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurologic) in the absence of other plausible diagnoses. Additional studies are needed to determine the full spectrum of this illness and its long-term effects on cardiac structure and function. Commentary from Dr. Shaji Menon (Salt Lake City, Utah), section editor of Pediatric Cardiology Journal Watch:   This retrospective multicenter study from 12 hospitals in France and 1 hospital in Switzerland presents data for children with acute left ventricular systolic dysfunction or cardiogenic shock and associated multisystem inflammatory syndrome between March 22 and April 30, 2020.  The inclusion criteria were the presence of fever (>38.5°C), cardiogenic shock, or acute left ventricular dysfunction (left ventricular ejection fraction <50%) with inflammatory state (C-reactive protein >100 mg/mL). 35 patients fulfilling the inclusion criteria with febrile cardiogenic shock or left ventricular dysfunction and inflammatory state were included in the study. All children presented with fever (>38.5°C). Gastrointestinal symptoms including abdominal pain, vomiting, or diarrhea present in majority (80%). Two patients underwent emergency operation for suspected appendicitis that was ultimately diagnosed as mesenteric adenolymphitis. Although clinical signs mimicking Kawasaki disease were common, including skin rash, cheilitis, cervical adenopathy, and meningism none of the patients met criteria for classic Kawasaki disease (Table 1). Only 6 patients complained of chest pain. The ECG was not specific, with ST-segment elevation in only 1 patient (Table 2). In a large proportion of patients, the hemodynamic presentation at admission to the pediatric ICU was shock with low systemic blood pressure. The median duration between the first clinical symptoms and symptoms of heart failure was 6 days (interquartile range, 4.5–6 days). Ventricular systolic dysfunction with global hypokinesia was common. One patient manifested takotsubo syndrome presentation with akinesis of the apical segment. Segmental hypokinesia and pericardial effusion was seen in 3 patients. Right ventricular systolic function was preserved in all patients. Dilatation of the coronary arteries (Z score >2 adjusted for body temperature) was found in 6 patients (17%), including 5 patients with dilatation of the left main stem and 1 patient with dilatation of the right coronary artery. The majority of patients received intravenous immunoglobulin (25 of 35 of patients). Twelve patients received intravenous steroids, 3 children received anakinra because of persistent severe inflammatory state and 23 of 35 patients were treated with therapeutic-dose heparin. Complete recovery of left ventricular systolic function was observed in 71% of patients. Five patients had residual mild to moderate left ventricular systolic dysfunction. None had a thrombotic or embolic event. Median ICU stay was 7 days (interquartile range, 3.7–10 days), and median hospital stay was 10 days (interquartile range, 8–14 days). Unlike patients with Kawasaki disease, median age of patients with MIS-C were older (10 years) and left ventricular dysfunction was more common at presentation. Maculopapular rash in a 12-year-old girl.