Comparison of Laboratory and Hemodynamic Time Series Data Across Original, Alpha, and Delta Variants in Patients With Multisystem Inflammatory Syndrome in Children.

OBJECTIVES: To compare the clinical, laboratory, and hemodynamic parameters during hospitalization for patients with multisystem inflammatory syndrome in children (MIS-C), across the Original/Alpha and the Delta variants of severe acute respiratory syndrome coronavirus 2 infection. DESIGN: Retrospective cohort study. SETTING: Single-center quaternary children's hospital. PATIENTS: Children with MIS-C admitted from May 2020 to February 2021(Original and Alpha variant cohort) and August 2021 to November 2021 (Delta variant cohort). MEASUREMENTS AND MAIN RESULTS: Continuous vital sign measurements, laboratory results, medications data, and hospital outcomes from all subjects were evaluated. Of the 134 patients (102 with Original/Alpha and 32 with Delta), median age was 9 years, 75 (56%) were male, and 61 (46%) were Hispanics. The cohort with Original/Alpha variant had more males (61% vs 41%; p = 0.036) and more respiratory/musculoskeletal symptoms on presentation compared with the Delta variant ( p < 0.05). More patients in the Original/Alpha variant cohort received mechanical ventilation (16 vs 0; p = 0.009). Median hospital length of stay (LOS) was 7 days, and ICU LOS was 3 days for the entire cohort. ICU LOS was shorter in cohort with the Delta variant compared with the Original/Alpha variant (4 vs 2 d; p = 0.001). Only one patient had cardiac arrest, two needed extracorporeal membrane oxygenation, and two needed left ventricular assist device (Impella, Danvers, MA), all in the Original/Alpha variant cohort; no mortality occurred in the entire cohort. MIS-C cohort associated with the Delta variant had lower INR, prothrombin time, WBCs, sodium, phosphorus, and potassium median values ( p < 0.05) during hospitalization compared with the Original/Alpha variants. Hemodynamic assessment showed significant tachycardia in the Original/Alpha variants cohort compared with the Delta variant cohort ( p < 0.05). INTERVENTIONS: None. CONCLUSIONS: Patients with MIS-C associated with the Delta variants had lower severity during hospitalization compared with the Original/Alpha variant. Analysis of distinct trends in clinical and laboratory parameters with future variants of concerns will allow for potential modification of treatment protocol.

Cardiovascular sequelae from COVID-19: perspectives from a paediatric cardiac ICU.

OBJECTIVE: Paediatric ICUs have shared the burden of the COVID-19 pandemic, including subspecialty cardiac ICUs. We sought to address knowledge gaps regarding patient characteristics, acuity, and sequelae of COVID-19 in the paediatric cardiac ICU setting. DESIGN: Retrospective review of paediatric cardiac ICU admissions with COVID-19-related disease. SETTING: Single centre tertiary care paediatric cardiac ICU. PATIENTS: All patients with PCR/antibody evidence of primary COVID-19 infection, and/or Multisystem Inflammatory Syndrome in Children, were admitted between 26 March, 2020 and 31 March, 2021. INTERVENTIONS: None. MAIN OUTCOMES MEASURES: Patient-level demographics, pre-existing conditions, clinical symptoms, and outcomes related to ICU admission were captured from medical records. RESULTS: Among 1064 patients hospitalised with COVID-19/Multisystem Inflammatory Syndrome in Children, 102 patients (9.5%) were admitted to cardiac ICU, 76 of which were symptomatic (median age 12.5 years [IQR 7.5-16.0]). The primary system involved at presentation was cardiovascular in 48 (63%). Vasoactive infusions were required in 62% (n = 47), with eight patients (11%) requiring VA ECMO. Severity of disease was categorised as mild/moderate in 16 (21%) and severe/critical in 60 patients (79%). On univariate analysis, African-American race, presentation with gastrointestinal symptoms or elevated inflammatory markers were associated with risk for severe disease. All-cause death was observed in five patients (7%, n = 5/72) with four patients remaining hospitalised at the time of data query. CONCLUSION: COVID-19 and its cardiovascular sequelae were associated with important morbidity and significant mortality in a notable minority of paediatric patients admitted to a paediatric cardiac ICU. Further study is required to quantify the risk of morbidity and mortality for COVID-19 and sequelae.

Lesion-Specific Congenital Heart Disease Mortality Trends in Children: 1999 to 2017.

OBJECTIVE: Congenital heart disease (CHD) is a leading cause of premature death in infants and children. Currently limited data are available regarding lesion specific mortality over time. Our study aimed to describe pediatric mortality trends by CHD lesion in the United States. METHODS: We conducted a 19 year analysis (1999 to 2017) of publicly available, deidentified multiple cause of death data compiled and produced by the National Center for Health Statistics. Analysis was stratified by CHD diagnosis and age using 3 age categories (infants, 1 to 4 years, and 5 to 17 years). Temporal trends of CHD mortality and the effect of contributing risk factors were analyzed by using joinpoint regression. RESULTS: Mortality was highest for in infants for all CHD lesions, in particular for total anomalous pulmonary venous return. Significant declines in infant CHD mortality occurred for most other lesions. Contributing risk factors, including prematurity, extracardiac birth defects, and genetic conditions, occurred in 19% of infant CHD deaths and demonstrated worse mortality trends in the majority of lesions. Mortality rates remained highest for single ventricle lesions in all ages, with an infant mortality rate plateau in the later half of the study and progressive increasing mortality rates for children 5 to 17 years. CONCLUSIONS: CHD mortality is decreasing for most lesions. Because of the heterogenicity of CHD lesions, there is expected variability in mortality trends by lesion and age group. Single ventricle lesions continue to contribute most heavily to premature death because of CHD demonstrated by significant increases in mortality rate for children aged 5 to 17 years.

Decreased Quality of Life in Children With Anomalous Aortic Origin of a Coronary Artery.

BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) is associated with sudden death in the young. We sought to determine quality of life (QOL) in patients/families affected by AAOCA. METHODS: Patients with AAOCA (8-18 years) were prospectively included from January 2016 to May 2017. Parent proxy and patient Pediatric Cardiac Quality of Life Inventory (PCQLI) were used to evaluate QOL and Pediatric Quality of Life Inventory (PedsQL) Family Impact Module to assess the impact of AAOCA on families, as primary outcomes. Secondary outcomes included peer relationship, anxiety, and depression assessed using patient-reported outcomes measurement information system. Patients deemed high-risk were offered surgery/exercise restriction. Generalized linear mixed regression models were used to determine significant predictors of outcomes. RESULTS: Fifty-three patients, the majority (n = 31, 59%) unrepaired, and 49 caregivers were included. Using PCQLI, patient and parent proxy QOL scores were similar to published scores for children with long-QT syndrome. Patients' QOL score was associated with exertional symptoms, perceived chronic disease, and altered parent's concentration ability. Likewise, parent proxy QOL scores were associated with mother's living situation, exertional symptoms, parent missing work for ≥1 day, and disturbed parental functioning at work. Family impact scores were associated with lower maternal education, among other measures. Risk categories or surgical status did not impact patient, parent proxy reported, or family impact QOL. CONCLUSION: Anomalous aortic origin of a coronary artery is associated with decreased QOL as perceived by patients and caregiver and is associated with numerous facets of family functioning. These findings are independent of risk categorization or surgical status.

The Kawasaki Disease Comparative Effectiveness (KIDCARE) trial: A phase III, randomized trial of second intravenous immunoglobulin versus infliximab for resistant Kawasaki disease.

BACKGROUND: Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease (KD), the most common cause of acquired heart disease in children, 10-20% of patients are IVIG-resistant and require additional therapy. This group has an increased risk of coronary artery aneurysms (CAA) and there has been no adequately powered, randomized clinical trial in a multi-ethnic population to determine the optimal therapy for IVIG-resistant patients. OBJECTIVES: The primary outcome is duration of fever in IVIG-resistant patients randomized to treatment with either infliximab or a second IVIG infusion. Secondary outcomes include comparison of inflammatory markers, duration of hospitalization, and coronary artery outcome. An exploratory aim records parent-reported outcomes including signs, symptoms and treatment experience. METHODS: The KIDCARE trial is a 30-site randomized Phase III comparative effectiveness trial in KD patients with fever ≥36 h after the completion of their first IVIG treatment. Eligible patients will be randomized to receive either a second dose of IVIG (2 g/kg) or infliximab (10 mg/kg). Subjects with persistent or recrudescent fever at 24 h following completion of the first study treatment will cross-over to the other treatment arm. Subjects will exit the study after their first outpatient visit (5-18 days following last study treatment). The parent-reported outcomes, collected daily during hospitalization and at home, will be compared by study arm. CONCLUSION: This trial will contribute to the management of IVIG-resistant patients by establishing the relative efficacy of a second dose of IVIG compared to infliximab and will provide data regarding the patient/parent experience of these treatments.