Contemporary Outcomes of Children With Acute Fulminant Myocarditis Supported With Peripheral Extracorporeal Membrane Oxygenation.

Despite extracorporeal membrane oxygenation (ECMO) utilization in nearly 20% of cases, there are limited data in children with acute fulminant myocarditis (AFM) requiring ECMO. Herein we identify risk factors for death or heart transplant (HT) in children with AFM supported with ECMO, describe our experience with left atrial (LA) decompression, and depict long-term outcomes of survivors. We performed a retrospective cohort of patients <18 years with AFM (≤14 days of symptoms, rapid cardiogenic shock, and normal left ventricular [LV] size on presentation) supported with ECMO admitted to a single intensive care unit from 1997 to 2021. Among 28 patients (median age 9 years), 21 (75%) survived to discharge without HT. Patients were supported on ECMO for a median of 6 days. Three patients were bridged to HT with durable ventricular assist devices (VAD). Four patients died, two of whom were supported with VAD. At presentation, seven (25%) patients had high grade or complete atrioventricular block and eight (29%) had ventricular tachycardia. Before ECMO cannulation, 21 (75%) patients received CPR. The death/HT group had higher peak troponin levels (12.5 vs . 1.0 ng/ml, p = 0.02) and initial mean LA or pulmonary capillary wedge pressure (27 vs . 18 mm Hg, p = 0.03). Left atrial decompression was performed in 22 patients (79%). Twenty-two (79%) had acute myocarditis on endomyocardial biopsy. Among transplant-free survivors, 18 (86%) had normalization in LV function (median 7 days); the remaining three patients had persistent mild LV dysfunction at last follow-up (median 842 days). Transplant-free survival of pediatric patients with AFM supported on ECMO was 75% and associated with lower initial LA pressure and lower peak troponin. Recovery in ventricular function among survivors was rapid and durable.

Higher Survival With the Use of Extracorporeal Cardiopulmonary Resuscitation Compared With Conventional Cardiopulmonary Resuscitation in Children Following Cardiac Surgery: Results of an Analysis of the Get With The Guidelines-Resuscitation Registry.

OBJECTIVES: Extracorporeal membrane oxygenation to support cardiopulmonary resuscitation (CPR) is increasingly used in children suffering cardiac arrest after cardiac surgery. However, its efficacy in promoting survival has not been evaluated. We compared survival of pediatric cardiac surgery patients suffering in-hospital cardiac arrest who were resuscitated with extracorporeal CPR (E-CPR) to those resuscitated with conventional CPR (C-CPR) using propensity matching. DESIGN: Retrospective study using multicenter data from the American Heart Association Get With The Guidelines-Resuscitation registry (2008-2020). SETTING: Multicenter cardiac arrest database containing cardiac arrest and CPR data from U.S. hospitals. PATIENTS: Cardiac surgical patients younger than 18 years old who suffered in-hospital cardiac arrest and received greater than or equal to 10 minutes of CPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1223 patients, 741 (60.6%) received C-CPR and 482 (39.4%) received E-CPR. E-CPR utilization increased over the study period ( p < 0.001). Duration of CPR was longer in E-CPR compared with C-CPR recipients (42 vs. 26 min; p < 0.001). In a propensity score matched cohort (382 E-CPR recipients, 382 C-CPR recipients), E-CPR recipients had survival to discharge (odds ratio [OR], 2.22; 95% CI, 1.7-2.9; p < 0.001). E-CPR survival was only higher when CPR duration was greater than 18 minutes. Propensity matched analysis using patients from institutions contributing at least one E-CPR case ( n = 35 centers; 353 E-CPR recipients, 353 C-CPR recipients) similarly demonstrated improved survival in E-CPR recipients compared with those who received C-CPR alone (OR, 2.08; 95% CI, 1.6-2.8; p < 0.001). CONCLUSIONS: E-CPR compared with C-CPR improved survival in children suffering cardiac arrest after cardiac surgery requiring CPR greater than or equal to 10 minutes.

Real-world use of apixaban for the treatment and prevention of thrombosis in children with cardiac disease.

BACKGROUND: Direct oral anticoagulants use in pediatric cardiology is poorly defined. OBJECTIVE: We present the largest experience of apixaban use in children with heart disease, using weight- and level-based dosing. METHODS: Retrospective single-center analysis of cardiac patients ≤19 years treated with apixaban. Patients were evaluated for safety (clinically relevant non-major [CRNM] or major bleeding; thrombotic events) and effectiveness (thrombus improvement by imaging). Peak drug-specific anti-Xa chromogenic assay results ("apixaban levels") were analyzed. RESULTS: Over 3 years (5/2018-9/2021), 219 children, median age 6.8 years (0.3-19), median weight 20.8 kg (4.8-160) received apixaban, totaling 50,916 patient days. Of them, 172 (79%) warranted thromboprophylaxis and 47 (21%) thrombosis treatment (with 10 arterial, 19 venous, 15 intracardiac, and 3 pulmonary). The median initial peak apixaban level was 165 ng/mL (23-474; n = 125) in the prophylaxis subgroup and 153 ng/mL (30-450; n = 33) in the treatment subgroup; dosage was adjusted in response to levels in 25% of the patients. There were 4 bleeding safety events (3 CRNM; 1 major, hemoptysis complicating empyema); the serious bleeding event rate was 2.9 per 100 patient-years of apixaban. Minor bleeding events (42) were noted in 18 patients, with an additional 2 having leukopenia, 1 transaminitis, and 3 rashes. An improvement in thrombosis was seen in 95% of the treated patients with available follow-up imaging (37/39 patients). CONCLUSION: Apixaban use was feasible with a low rate of adverse events across a diverse pediatric cardiac population using commercially available tablets dosed to weight and adjusted based on peak apixaban levels.

Apixaban Anticoagulation in Children and Young Adults Supported With the HeartMate 3 Ventricular Assist Device.

There is a growing population of pediatric and adult patients supported with the HeartMate 3 ventricular assist device (HM3 VAD) all of whom require anticoagulation. Apixaban is an anticoagulant requiring less testing than warfarin which has been shown to be effective in other indications. We report five pediatric and young adult patients managed on HM3 VAD with apixaban anticoagulation for 1589 days of VAD support between January 6, 2019 and January 7, 2022. The median age was 17 years and the weight was 69 kg. Four patients had congenital heart disease (2 single-ventricle Fontan circulation, and 2 biventricular circulations) and one had dilated cardiomyopathy. Apixaban was initiated at a median of 7 days postoperatively and doses were titrated based on peak apixaban-specific anti-Xa chromogenic analysis levels (goal 150-250 ng/ml). All patients received aspirin 81 mg daily. There was one major hemocompatibility-related event observed (outflow graft thrombus in the setting of medication nonadherence and chronic VAD infection); there was no major bleeding, death, or stroke. Three patients underwent heart transplantation and two remain on VAD support. In this limited series, apixaban paired with a level-based dosing regimen and low-dose aspirin provided safe and effective antithrombosis with only one hemocompatibility-related event related to medication non-adherence.

Rheumatic Heart Disease in the United States: Forgotten But Not Gone: Results of a 10 Year Multicenter Review.

Background Recent evaluation of rheumatic heart disease (RHD) mortality demonstrates disproportionate disease burden within the United States. However, there are few contemporary data on US children living with acute rheumatic fever (ARF) and RHD. Methods and Results Twenty-two US pediatric institutions participated in a 10-year review (2008-2018) of electronic medical records and echocardiographic databases of children 4 to 17 years diagnosed with ARF/RHD to determine demographics, diagnosis, and management. Geocoding was used to determine a census tract-based socioeconomic deprivation index. Descriptive statistics of patient characteristics and regression analysis of RHD classification, disease severity, and initial antibiotic prescription according to community deprivation were obtained. Data for 947 cases showed median age at diagnosis of 9 years; 51% and 56% identified as male and non-White, respectively. Most (89%) had health insurance and were first diagnosed in the United States (82%). Only 13% reported travel to an endemic region before diagnosis. Although 96% of patients were prescribed secondary prophylaxis, only 58% were prescribed intramuscular benzathine penicillin G. Higher deprivation was associated with increasing disease severity (odds ratio, 1.25; 95% CI, 1.08-1.46). Conclusions The majority of recent US cases of ARF and RHD are endemic rather than the result of foreign exposure. Children who live in more deprived communities are at risk for more severe disease. This study demonstrates a need to improve guideline-based treatment for ARF/RHD with respect to secondary prophylaxis and to increase research efforts to better understand ARF and RHD in the United States.

Parent-Reported Symptoms and Perceived Effectiveness of Treatment in Children Hospitalized with Advanced Heart Disease.

OBJECTIVE: To characterize parent-reported symptom burden and effectiveness of symptom management in children hospitalized with advanced heart disease. STUDY DESIGN: Prospective survey study of 161 parents whose child was admitted to a single institution with advanced heart disease between March 2018 and February 2019 using the Survey about Caring for Children with Heart Disease. RESULTS: Of the 161 patients, 54% were under 2 years old with a diagnosis of single ventricle physiology (39%), pulmonary hypertension (12%), and other congenital heart disease (28%). Over one-half (56%) of parents reported that their child was experiencing a high degree ("a great deal"/"a lot") of symptoms. The most frequently reported symptoms were pain (68%), fatigue (63%), and breathing difficulties (60%). Of the symptoms that were treated, parents perceived successful treatment to be least likely for their child's sleep disturbance (24%), depression (29%), and fatigue (35%). Parents who reported their child's functional status as New York Heart Association class III/IV were more likely to report that their child was experiencing "a great deal" of symptoms, compared with those who reported class I/II (51% vs 19%, P < .001). Parents who reported their child was experiencing a high degree of suffering from fatigue were also more likely to report a high symptom burden (P < .001). CONCLUSIONS: Parents of children with advanced heart disease reported high symptom burden with a broad spectrum of symptoms. Parents reported fatigue and psychiatric symptoms frequently and rarely reported treatment as successful. Parents' view of their child's symptom burden was concordant with their perception of their child's functional status.

Detailed Assessment of Left Ventricular Function in Multisystem Inflammatory Syndrome in Children, Using Strain Analysis.

BACKGROUND: Cardiac manifestations in multisystem inflammatory syndrome in children (MIS-C) occur in ∼80% of patients. Left ventricular (LV) systolic dysfunction is the most frequent cardiac finding. METHODS: In this single-centre, retrospective cohort study, we report on detailed assessment of LV function in MIS-C patients using strain and strain rate analysis. We compare those with normal peak systolic strain z-scores (both longitudinal and circumferential strain) to those with abnormal peak systolic strain z-scores (decreased circumferential and/or longitudinal strain). RESULTS: Among 25 patients, 14 (56%) were male, 20 (80%) were Black or Hispanic, 13 (52%) were overweight/obese, and the median age was 11.4 years (interquartile range: 7.5 to 16). Median ejection fraction (EF) was 55.2% (interquartile range: 48.3% to 58%), with the abnormal strain patients having a lower EF (P < 0.01). Demographics were similar between groups. The abnormal strain patients had more organ systems involved and were more likely to require inotropic support. In a comparison of MIS-C patients with normal EF (n = 15) to controls, MIS-C patients had lower peak systolic strain as well as lower early diastolic strain rates. In patients with initially depressed function, EF normalized in 8 of 10 (80%), but 4 of 11 (36%) patients had persistently abnormal systolic strain after discharge. CONCLUSIONS: LV systolic dysfunction is common in the acute phase of MIS-C, and detection may be improved with strain imaging. Longitudinal cardiac follow-up is imperative, as some patients may be at risk for persistent LV dysfunction.

CONTEXTE: Des manifestations cardiaques sont observées chez environ 80 % des patients atteints du syndrome inflammatoire multisystémique de l'enfant (SIM-E). La dysfonction systolique ventriculaire gauche est le problème cardiaque observé le plus fréquemment. MÉTHODOLOGIE: Dans cette étude de cohorte rétrospective et unicentrique, nous rapportons les résultats d'une évaluation détaillée de la fonction ventriculaire gauche chez des patients atteints du SIM-E sous l'angle de l'étude des contraintes et des taux de contrainte. Nous comparons les patients dont les écarts z des pics de contrainte systolique sont normaux (contraintes tant longitudinales que circonférentielles) et ceux dont les écarts z des pics de contrainte systolique sont anormaux (réduction de la contrainte circonférentielle ou longitudinale). RÉSULTATS: Sur 25 patients, 14 (56 %) étaient de sexe masculin, 20 (80 %) étaient noirs ou hispaniques, 13 (52 %) étaient en surpoids ou obèses, et l'âge médian était de 11,4 ans (intervalle interquartile : de 7,5 à 16). La fraction d'éjection (FE) médiane était de 55,2 % (intervalle interquartile : de 48,3 % à 58 %), et était moins élevée chez les patients présentant une contrainte anormale (p < 0,01). Les caractéristiques démographiques étaient comparables dans tous les groupes. Les patients chez lesquels la contrainte était anormale présentaient un plus grand nombre d'organes atteints et étaient plus susceptibles de nécessiter un soutien inotrope. Comparativement au groupe témoin, les patients SIM-E ayant une FE normale (n = 15) présentaient un pic de contrainte systolique moins élevé et des taux de contrainte diastolique précoce plus faibles. Chez les patients dont la fonction était déprimée à l'origine, la FE s'est normalisée chez huit patients sur 10 (80 %), mais quatre sur 11 (36 %) présentaient une contrainte systolique persistant après leur sortie de l'hôpital. CONCLUSIONS: La dysfonction systolique ventriculaire gauche est fréquente dans la phase aiguë du SIM-E, et son repérage pourrait être amélioré par l'imagerie permettant de visualiser les contraintes. Un suivi cardiaque longitudinal est impératif, car certains patients peuvent être à risque de souffrir d'une dysfonction ventriculaire gauche persistante.

Socioeconomic and Racial and/or Ethnic Disparities in Multisystem Inflammatory Syndrome.

OBJECTIVES: To characterize the socioeconomic and racial and/or ethnic disparities impacting the diagnosis and outcomes of multisystem inflammatory syndrome in children (MIS-C). METHODS: This multicenter retrospective case-control study was conducted at 3 academic centers from January 1 to September 1, 2020. Children with MIS-C were compared with 5 control groups: children with coronavirus disease 2019, children evaluated for MIS-C who did not meet case patient criteria, children hospitalized with febrile illness, children with Kawasaki disease, and children in Massachusetts based on US census data. Neighborhood socioeconomic status (SES) and social vulnerability index (SVI) were measured via a census-based scoring system. Multivariable logistic regression was used to examine associations between SES, SVI, race and ethnicity, and MIS-C diagnosis and clinical severity as outcomes. RESULTS: Among 43 patients with MIS-C, 19 (44%) were Hispanic, 11 (26%) were Black, and 12 (28%) were white; 22 (51%) were in the lowest quartile SES, and 23 (53%) were in the highest quartile SVI. SES and SVI were similar between patients with MIS-C and coronavirus disease 2019. In multivariable analysis, lowest SES quartile (odds ratio 2.2 [95% confidence interval 1.1-4.4]), highest SVI quartile (odds ratio 2.8 [95% confidence interval 1.5-5.1]), and racial and/or ethnic minority background were associated with MIS-C diagnosis. Neither SES, SVI, race, nor ethnicity were associated with disease severity. CONCLUSIONS: Lower SES or higher SVI, Hispanic ethnicity, and Black race independently increased risk for MIS-C. Additional studies are required to target interventions to improve health equity for children.

Transcription factor NF-κB in a basal metazoan, the sponge, has conserved and unique sequences, activities, and regulation.

Herein, we characterize transcription factor NF-κB from the demosponge Amphimedon queenslandica (Aq). Aq-NF-κB is most similar to NF-κB p100/p105 among vertebrate proteins, with an N-terminal DNA-binding domain, a C-terminal Ankyrin (ANK) repeat domain, and a DNA binding-site profile akin to human NF-κB proteins. Like mammalian NF-κB p100, C-terminal truncation allows nuclear translocation of Aq-NF-κB and increases its transcriptional activation activity. Expression of IκB kinases (IKKs) induces proteasome-dependent C-terminal processing of Aq-NF-κB in human cells, and processing requires C-terminal serines in Aq-NF-κB. Unlike NF-κB p100, C-terminal sequences of Aq-NF-κB do not inhibit its DNA-binding activity. Tissue of a black encrusting demosponge contains NF-κB site DNA-binding activity, as well as nuclear and processed NF-κB. Treatment of sponge tissue with LPS increases both DNA-binding activity and processing of NF-κB. A. queenslandica transcriptomes contain homologs to upstream NF-κB pathway components. This is first functional characterization of NF-κB in sponge, the most basal multicellular animal.

Pediatric survivors of out-of-hospital ventricular fibrillation: Etiologies and outcomes.

BACKGROUND: In general, the prognosis is poor for pediatric patients who experience out-of-hospital (OOH) cardiac arrest, with survival rates of 12% to 29%. OBJECTIVE: The purpose of this study was to describe the causes and outcomes of pediatric patients with documented ventricular fibrillation (VF) at resuscitation from OOH cardiac arrest with sustained return of spontaneous circulation after defibrillation and survival to hospital admission. METHODS: Retrospective analysis of OOH-VF patients <19 years of age evaluated between 2004 and 2016 was performed. Primary outcome measures included demographics, arrest and resuscitation parameters, cardiac diagnoses, survival, and neurologic outcome. RESULTS: Forty-five patients fulfilled study criteria (median age 12 years; range 2 months to 18 years). Cardiac arrest occurred in public in 68% of cases, with bystander cardiopulmonary resuscitation in 42% before arrival of emergency medical services. All patients underwent defibrillation (1-6 shocks) with return of spontaneous circulation and survival to hospital admission. Underlying etiologies were primary electrical disease (33%), cardiomyopathy (27%), congenital heart disease (11%), other (13%), and unknown (16%). Before arrest, 40% of patients had a cardiac diagnosis and 26% had symptoms. Ultimately, 40 of 45 patients (89%) survived resuscitation to hospital discharge. During 72 ± 37 months of follow-up, 38% of survivors had a normal neurologic outcome, whereas 32% had mild neurologic impairment and 30% had moderate-to-severe neurologic impairment. CONCLUSION: In pediatric patients resuscitated from OOH-VF, a cardiovascular cause was identified in >80%. Regardless of cause, survival and neurologic prognosis appear improved compared to patients with asystole or pulseless electrical activity. These findings support early rhythm assessment and advanced cardiopulmonary resuscitation protocols in pediatric cardiac arrest victims.

Association of elevated triglycerides and acute myocardial infarction in young Hispanics.

BACKGROUND: Previous studies have demonstrated that acute myocardial infarction (AMI) in young patients (age <45years) is associated with a high prevalence of smoking, obesity, hyperlipidemia and single vessel coronary artery disease (CAD). Hispanics represent the largest growing ethnic minority in the United States, yet features of AMI in young Hispanics have not been described. METHODS: Patients undergoing percutaneous coronary intervention for AMI at Los Angeles County + University of Southern California Medical Center and Keck Medical Center were studied. We compared young Hispanics (age<45, n=47) with older patients (Hispanics and non-Hispanics age ≥45, n=888) to identify unique features of AMI in young Hispanics. We also compared young Hispanics with young non-Hispanics (n=33) and older Hispanics (n=447) in regards to traditional CAD risk factors, laboratory values and in-hospital outcomes. Multivariable logistic regression was performed to identify variables independently associated with in-hospital mortality. RESULTS: Young Hispanics had higher triglyceride levels than young non-Hispanics and older patients (234.5±221.0mg/dL vs. 145.3±67.4mg/dL vs. 156±118.2mg/dL, p<0.0004); and higher triglyceride than older Hispanics (234.5±221.0 vs. 147.0±98.9mg/dL, p<0.02). Body mass index was independently associated with the logarithm (base10) of triglyceride levels (p<0.0001). Hispanic ethnicity and age<45years, however, were not independently associated with in-hospital mortality. CONCLUSIONS: Young Hispanics with AMI have higher triglyceride levels than young non-Hispanics and older Hispanics. The elevated triglyceride levels may be related to lifestyle changes experienced by a young immigrant population transitioning to life in the United States.