Comparison of Adverse Clinical Outcomes in Children Hospitalized for Myocarditis with and Without COVID-19.

We used a nationally representative database of the US, which included 1995 myocarditis cases, among whom 620 children had COVID-19. While the risk of in-hospital mortality was not higher, illness severity and length of hospital stay were higher in patients with myocarditis and COVID-19 than those without COVID-19.

Impact of congenital heart disease on outcomes among pediatric patients hospitalized for COVID-19 infection.

BACKGROUND: COVID-19 infection is generally regarded as an acute self-limiting illness in children, but it can cause significant morbidity and mortality in both healthy and high-risk children. There are limited data on the outcomes of children with congenital heart disease (CHD) and COVID-19. This study aimed to examine the risks of mortality, in-hospital cardiovascular and non-cardiovascular complications in this patient population. METHODS: We analyzed data from hospitalized pediatric patients from 2020 using the nationally representative National Inpatient Sample (NIS). Children hospitalized for COVID-19 were included, and weighted data were used to compare in-hospital mortality and morbidities between children with and without CHD. RESULTS: Out of 36,690 children admitted with a diagnosis of COVID-19 infection(ICD-10 code:U07.1 and B97.29) during calendar year 2020, 1240 (3.4%) had CHD. The risk of mortality in children with CHD was not significantly higher than those without CHD(1.2% vs. 0.8%, p = 0.50), with adjusted OR (aOR) of 1.7 (95% CI: 0.6-5.3). Tachyarrhythmias and heart block were more likely in CHD children with an aOR of 4.2 (95% CI: 1.8-9.9) and aOR of 5.0 (95% CI: 2.4-10.8), respectively. Similarly, respiratory failure [aOR = 2.0 (1.5-2.8)], respiratory failure requiring non-invasive mechanical ventilation [aOR = 2.7 (1.4-5.2)] and invasive mechanical ventilation [aOR = 2.6 (1.6-4.0)], and acute kidney injury [aOR = 3.4 (2.2-5.4)] were all significantly higher among patients with CHD. Median length of hospital stay in children with CHD was longer than those without CHD [5 days (IQR: 2-11) vs. 3 days (IQR: 2-5), p = < 0.001]. CONCLUSIONS: Children with CHD hospitalized with COVID-19 infection were at increased risk of serious cardiovascular and non-cardiovascular adverse clinical outcomes. They also had increased length of hospital stay and utilization of healthcare resources.

Identification of prognostic factors for pediatric myocarditis with a random forests algorithm-assisted approach.

BACKGROUND: Pediatric myocarditis is a rare disease with substantial mortality. Little is known regarding its prognostic factors. We hypothesize that certain comorbidities and procedural needs may increase risks of poor outcomes. This study aims to identify prognostic factors for pediatric myocarditis. METHODS: The national Kids' Inpatient Database was used in the study. A random forests algorithm was implemented for mortality prediction based on comorbidities and procedures. Linear regression analysis was then performed to quantify their associations with mortality and length of stay. RESULTS: The prevalence of pediatric myocarditis among all pediatric hospitalizations doubled from 2003 to 2016. The mortality rate peaked in 2006 (6.7%) and declined steadily thereafter, with a rate of 3.2% in 2016. Brain injury (including encephalopathy, cerebral edema, and intracranial hemorrhage), acute kidney injury, dysrhythmias, coagulopathy, sepsis, and ECMO use were all independent prognostic factors associated with increased mortality and prolonged hospital stay. CONCLUSION: Prognostic factor identification may not be straightforward in rare diseases such as pediatric myocarditis due to small cohort size in each treating facility. Findings from this report provide insights into the prognostic factors for pediatric myocarditis, and may allow clinicians to be better prepared when informing patients and their families regarding disease outcomes. IMPACT: The rate of hospitalization due to pediatric myocarditis was increasing but the mortality rate was declining over the past decade. End organ damage, including the brain and the kidney, was associated with mortality and prolonged hospital stay in pediatric myocarditis. Tachyarrhythmias and cardiac function compromise requiring ECMO were also associated with mortality and prolonged hospital stay. A data science approach combining machine learning algorithms and conventional regression modeling using a large dataset may facilitate risk factor identification and outcome correlation in rare diseases, as illustrated in this study.

Impact of congenital heart disease on outcomes among pediatric patients hospitalized for influenza infection.

BACKGROUND: Young children and those with chronic medical conditions are at risk for complications of influenza including cardiopulmonary compromise. Here we aim to examine risks of mortality, clinical complications in children with congenital heart disease (CHD) hospitalized for influenza. METHODS: We analyzed data from in-hospital pediatric patients from 2003, 2006, 2009, 2012 and 2016 using the nationally representative Kids Inpatient Database (KID). We included children 1 year and older and used weighted data to compare the incidence of in-hospital mortality and rates of complications such as respiratory failure, acute kidney injury, need for mechanical ventilation, arrhythmias and myocarditis. RESULTS: Data from the KID estimated 125,470 children who were admitted with a diagnosis of influenza infection. Out of those, 2174(1.73%) patients had discharge diagnosis of CHD. Children with CHD who required hospitalization for influenza had higher in-hospital mortality (2.0% vs 0.5%), with an adjusted OR (aOR) of 2.8 (95% CI: 1.7-4.5). Additionally, acute respiratory failure and acute kidney failure were more likely among patients with CHD, with aOR of 1.8 (95% CI: 1.5-2.2) and aOR of 2.2 (95% CI: 1.5-3.1), respectively. Similarly, the rate of mechanical ventilatory support was higher in patients with CHD compared to those without, 14.1% vs 5.6%, aOR of 1.9 (95% CI: 1.6-2.3). Median length of hospital stay in children with CHD was longer than those without CHD [4 (IQR: 2-8) days vs. 2 (IQR: 2-4) days]. Outcomes were similar between those with severe vs non-severe CHD. CONCLUSIONS: Children with CHD who require hospital admission for influenza are at significantly increased risk for in-hospital mortality, morbidities, emphasizing the need to reinforce preventative measures (e.g. vaccination, personal hygiene) in this particularly vulnerable population.

22q11.2 Deletion Status Influences Resource Utilization in Infants Requiring Repair of Tetralogy of Fallot and Common Arterial Trunk.

22q11.2 deletion syndrome leads to both cardiac and non-cardiac developmental defects. We aimed to study the impact of 22q11.2 deletion syndrome on in-hospital outcomes in children undergoing surgical repair for tetralogy of Fallot (TOF) and truncus arteriosus (TA). Using the nationally representative Kids Inpatient Database (KID), we analyzed data from in-hospital pediatric patients for the years 2003, 2006, 2009, and 2012. We compared the in-hospital outcomes between those with and those without 22q11.2 deletion syndrome. There were 6126 cases of TOF and 968 cases of TA. 22q11.2 deletion syndrome were documented in 7.2% (n = 441) of the TOF and 27.4% (n  =  265) of the TA group. 22q11.2 deletion did not significantly increase the risk of mortality in either group: [OR = 1.98 (95% CI 0.99-3.94), adjusted p  =  0.053] for TOF and OR = 1.07 (95% CI 0.57-1.99), adjusted p = 0.82 for TA. However, the length of hospitalization was longer in the 22q11.2 deletion group by 8.6 days (95% CI 5.2-12), adjusted p < 0.001 for TOF and by 8.15 days (95% CI 1.05-15.25), adjusted p = 0.025 for the TA group. Acute respiratory failure [10.6% vs 5.5%, p < 0.001] and acute renal failure [6.3% vs 2.6%, p < 0.001] were higher in 22q11.2 deletion cohort within the TOF group but not in the TA group. Though survival is not affected, children with 22q11.2 deletion syndrome who undergo surgical repair for TOF and TA use significantly more hospital resources-specifically longer hospital stay and higher hospitalization cost-than those without 22q11.2 deletion syndrome. Prenatal or preoperative testing for 22q11deletion is indicated to make appropriate adjustments in parental, caregiver, and administrative expectations.

The Significance of Left Axis Deviation in the Pediatric Population: A Meta-Analysis.

Left axis deviation (LAD) in children is rare but may be associated with structural heart disease. The aim of this study is to systematically assess the significance of LAD in the pediatric population. We included studies listed in PubMed, EMBASE, Web of Science, Cochrane databases, and Google Scholar before May 31, 2018 and their reference lists. Nine selected studies were grouped into two categories: (1) prevalence of heart diseases in children with LAD on ECG and (2) prevalence of LAD in children with healthy hearts. Two authors independently extracted data using a standardized data extraction form. We identified nine studies including 7514 subjects. Among children with LAD, 66.3% (95% CI 36.9-86.9%) had heart disease. There was heterogeneity amongst studies with Q-value of 142.5 and I2 of 97.2%. The mean LAD rate was 1.6% in children with healthy hearts with 95% CI (0.4-2.2%) with Q-value of 11.8, I2 66.3% and T 0.34 with p value of 0.018. The limitation of study is that the included studies spanned 7 decades from the 1950s to 2018. Primary diagnostic modalities have evolved over time and the definition of LAD also varied among studies. In conclusion, LAD is associated with children with heart diseases, but may also be observed in healthy children. The degree of LAD axis correlated with the likelihood of congenital heart disease (CHD). Physical examination is crucial for identifying CHD in individuals with LAD.

An update on the epidemiology, length of stay, and cost of Kawasaki disease hospitalisation in the United States.

BACKGROUND: Kawasaki disease is an acute vasculitis of childhood and is the leading cause of acquired heart disease in the developed countries. METHODS: Data from hospital discharge records were obtained from the National Kids Inpatient Database for years 2009 and 2012. Hospitalisations by months, hospital regions, timing of admission, insurance types, and ethnicity were analysed. Length of stay and total charges were also analysed. RESULTS: There were 10,486 cases of Kawasaki disease from 12,678,005 children hospitalisation. Kawasaki disease was more common between 0 and 5 years old, in male, and in Asian. The January-March quarter had the highest rate compared to the lowest in the July-September quarter (OR=1.62, p < 0.001). Admissions on the weekend had longer length of stay [4.1 days (95 % CI: 3.97-4.31)] as compared to admissions on a weekday [3.72 days (95 % CI: 3.64-3.80), p < 0.001]. Blacks had the longest length of stay and whites had the shortest [4.33 days (95 % CI: 4.12-4.54 days) versus 3.60 days (95 % CI: 3.48-3.72 days), p < 0.001]. Coronary artery aneurysm was identified in 2.7 % of all patients with Kawasaki disease. Children with coronary artery aneurysm were hospitalised longer and had higher hospital charge. Age, admission during weekend, and the presence of coronary artery aneurysm had significant effect on the length of stay. CONCLUSIONS: This report provides the most updated epidemiological information on Kawasaki disease hospitalisation. Age, admissions during weekend, and the presence of coronary artery aneurysm are significant contributors to the length of stay.

Efficacy of prophylactic dexmedetomidine in preventing postoperative junctional ectopic tachycardia in pediatric cardiac surgery patients: A systematic review and meta-analysis.

BACKGROUND: Junctional ectopic tachycardia is a serious tachyarrhythmic complication following pediatric cardiac surgery. It is difficult to manage and is associated with significant morbidity and mortality. Conventional nonpharmacological and pharmacological measures have shown limited effects. Dexmedetomidine is an α2 agonist which has recently been shown in multiple studies to be effective. AIMS: The aim of this systematic review with meta-analysis was to evaluate the efficacy of prophylactic dexmedetomidine administration in the prevention of junctional ectopic tachycardia in pediatric patients following cardiac surgeries. METHODS: We searched MEDLINE, EMBASE, Cochrane, Web of Science, and relevant references published in English before December 20, 2017 and performed meta-analysis on the selected studies, with one group receiving prophylactic perioperative dexmedetomidine administration and another group receiving placebo. The primary outcome was the incidence of junctional ectopic tachycardia, secondary outcomes included bradycardia, hypotension, intensive care unit stay, total hospital stay, inotropic scores, and total mechanical ventilation time. Odds ratio or mean difference with 95% confidence intervals were calculated using a random effect model. RESULTS: Seven studies (5 prospective randomized studies and 2 retrospective case-controlled studies) with a total of 1616 patients were analyzed. The incidence of junctional ectopic tachycardia in the dexmedetomidine group was significantly reduced compared to placebo. Similarly, intensive care unit stay, inotropic scores, and total mechanical ventilation time were also significantly decreased in the dexmedetomidine group. No significant increases in adverse events were found. Mortality was low in both groups. CONCLUSION: Prophylactic dexmedetomidine is effective in reducing the incidence of postoperative junctional ectopic tachycardia without significant increases in adverse events in pediatric patients undergoing surgery for congenital heart diseases.

Variation in the α(2A) adrenoceptor gene and the effect of dexmedetomidine on plasma insulin and glucose.

OBJECTIVES: Sympathetic activation inhibits insulin secretion through activation of pancreatic α(2)A adrenoreceptors (α(2A)ARs). A common genetic α(2A)AR variant (rs553668) is associated with impaired insulin secretion. α(2A)R agonists would be expected to decrease insulin secretion, but their effects on glucose homeostasis in humans are poorly characterized. We examined the hypotheses that the selective α(2A)R agonist, dexmedetomidine, decreases plasma insulin levels and increases plasma glucose levels in humans and that these effects are modified by genetic α(2A)AR variants. METHODS: Healthy, fasting, White (n=31) and Black (n=33) participants aged between 18 and 45 years received three sequential infusions of placebo (normal saline) at 30-min intervals, followed by three infusions of dexmedetomidine (0.1, 0.15, and 0.15 mcg/kg). Plasma insulin and glucose concentrations were measured at baseline and after the administration of placebo and dexmedetomidine. We genotyped ADRA2A rs553668 and rs2484516, which characterize haplotypes 4 and 4b, respectively. RESULTS: Dexmedetomidine decreased fasting insulin concentrations by 37%, from a median value after placebo administration of 7.9 µU/ml (interquartile range: 6.0-12.6) to 4.9 µU/ml (interquartile range: 3.5-7.9; P<0.001). Plasma glucose concentrations increased from 76±6 to 79±7 mg/dl (P<0.001). The rs2484516 variant allele was associated with higher baseline insulin concentrations before (P=0.001) and after adjustment for potential confounders (P=0.014) and a greater decrease in insulin concentration after dexmedetomidine administration (P=0.016), which was no longer significant after adjustment for baseline concentrations and other confounders (P=0.58). CONCLUSION: Low-dose dexmedetomidine decreased plasma insulin concentration and mildly increased plasma glucose concentration in healthy fasting individuals. The ADRA2A genetic variation may affect baseline insulin concentrations and thus the insulin decrease after dexmedetomidine administration.

Catecholamine pathway gene variation is associated with norepinephrine and epinephrine concentrations at rest and after exercise.

OBJECTIVE: To examine the hypothesis that genetic variation in enzymes and transporters associated with synthesis, storage, release, and metabolism of catecholamines contributes to the interindividual variability in plasma catecholamine concentrations at rest and after exercise. METHODS: We measured plasma norepinephrine (NE) and epinephrine concentrations at rest and after a standardized exercise protocol in 165 healthy individuals (60% White, 40% African-American) and examined 29 functional or common variants in 14 genes involved in synthesis, transport, or metabolism of catecholamines. We examined the relationship between genotypes and NE concentrations at rest and the increase after exercise (ΔNE) by multiple linear regression with adjustment for covariates [age, race, sex, BMI, fitness, and resting NE (for ΔNE)]. As a secondary outcome, we carried out similar analyses for epinephrine concentrations. RESULTS: There was large interindividual variability in resting NE (mean, 204±102 pg/ml; range, 39-616 pg/ml) and ΔNE (mean, 256±206 pg/ml; range, -97 to 953 pg/ml). Resting NE was significantly associated with variants of four genes: CYB561 (P<0.001), VMAT2 (P=0.016), CHGA (P=0.039), and PNMT (P=0.038). ΔNE after exercise was associated with three variants of PNMT (P=0.041) and COMT (P=0.033 and 0.035), and resting and exercise epinephrine concentrations were associated with two variants each. CONCLUSION: The findings of this exploratory study suggest that variation in catecholamine pathway genes contributes to the interindividual variability in plasma NE and epinephrine concentrations at rest and after exercise.

In-Hospital Outcomes in Fontan Completion Surgery According to Age.

Actual timing of the Fontan operation is variable. Our aim was to evaluate the impact of age at the time of Fontan operation on mortality and clinical outcome and characterize patients with worse outcomes. We conducted a retrospective, cross-sectional study on the Fontan operation using nationally representative databases from 2003 to 2016 and categorized the patient into 1 of 5 groups according to their age at the time of surgery: <2, 2, 3, 4, and ≥5 years. Survey-weighted logistic regression models were used to compare the outcomes of the different age groups. A total of 6,647 children underwent the Fontan completion procedure during the study period with median age 3 (interquartile range 2 to 4) years. The in-hospital mortality was 2.1%. In logistic regression models, in-hospital mortality, respiratory failure, acute kidney injury, chylothorax, arrhythmias, and sudden cardiac arrest were similar among the 5 age groups. Compared with children >2 years, those <2 years were less likely to be admitted for surgery on an elective basis (73.5% vs 90.4%, p <0.001), more likely to have chromosomal anomalies (2.7% vs 1.7%), and more likely to have repair of atrioventricular valves (8.5% vs 6.0%, p = 0.027). Mortality was higher in those with an underlying atrioventricular septal defect (AVSD) adjusted odds ratio 4.3 (2.4 to 7.9, p <0.001). Repair of AV valves was more common in the AVSD group compared with those in non-AVSD (14.3% vs 5.5%, p <0.001). In conclusion, age at Fontan completion does not adversely affect the in-hospital outcomes. Our focus should be on optimizing essential factors that are crucial for successful Fontan completion.

Machine Learning for Mortality Prediction in Pediatric Myocarditis.

Background: Pediatric myocarditis is a rare disease. The etiologies are multiple. Mortality associated with the disease is 5-8%. Prognostic factors were identified with the use of national hospitalization databases. Applying these identified risk factors for mortality prediction has not been reported. Methods: We used the Kids' Inpatient Database for this project. We manually curated fourteen variables as predictors of mortality based on the current knowledge of the disease, and compared performance of mortality prediction between linear regression models and a machine learning (ML) model. For ML, the random forest algorithm was chosen because of the categorical nature of the variables. Based on variable importance scores, a reduced model was also developed for comparison. Results: We identified 4,144 patients from the database for randomization into the primary (for model development) and testing (for external validation) datasets. We found that the conventional logistic regression model had low sensitivity (~50%) despite high specificity (>95%) or overall accuracy. On the other hand, the ML model struck a good balance between sensitivity (89.9%) and specificity (85.8%). The reduced ML model with top five variables (mechanical ventilation, cardiac arrest, ECMO, acute kidney injury, ventricular fibrillation) were sufficient to approximate the prediction performance of the full model. Conclusions: The ML algorithm performs superiorly when compared to the linear regression model for mortality prediction in pediatric myocarditis in this retrospective dataset. Prospective studies are warranted to further validate the applicability of our model in clinical settings.

Socioeconomic and racial disparities in the prevalence of congenital heart disease in infants of diabetic mothers.

Infants of diabetic mothers (IDM) are at increased risk for congenital heart disease (CHD). There is little information in the literature about the impact of economic status and race/ethnicity on the prevalence of CHD in IDM. Using the KID national database collected from 2003 to 2012, we studied over 180,000 IDM to compare the prevalence of CHD according to family income and race/ethnicity. There were 9214 (5.02%) CHDs out of 183 453 IDM. We found significant impact of family income and race/ethnicity on the prevalence of CHD. Specifically, compared to IDM born in a family with highest 25th quartile family income, infants in the lowest 25th quartile family income had higher odds of CHD with unadjusted odds ratio (OR) of 1.6 [(95% confidence interval (CI): 1.4-1.7), p < .001]. In terms of racial/ethnic differences, Black [unadjusted OR = 1.4 (95% CI: 1.3-1.5), p < .001] and Hispanic [unadjusted OR 1.26 (95% CI: 1.2-1.4), p < .001] IDM are more likely, and Asians [0.69 (95% CI: 0.59-0.81), p < .001] were less likely to have CHD when compared to whites. When adjusting race/ethnicity for family income quartile and vice versa, we did not observe changes in the estimates, suggesting that family income and race/ethnicity impact on the odds of CHD independently. Our report of higher prevalence of CHD among IDM in ethnic minorities and lower socioeconomic status would warrant more studies to further dissect causes of higher prevalence in these subpopulations.

Socioeconomic and racial disparities in the risk of congenital anomalies in infants of diabetic mothers: A national population-based study.

We used a national population-based database to study socioeconomic and racial disparities associated with congenital anomalies in 293,498 infants of diabetic mothers. Risk of anomalies in infants of diabetic mothers was highest in poor families (13.3%) compared to the rich families (10.9%), and black families had the highest risk of anomalies (14.0%) compared to white families (11.8%).

Comparison of In-Hospital Outcomes When Repair of Tetralogy of Fallot Is in the Neonatal Period Versus in the Post-Neonatal Period.

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease (CHD) and optimal timing for total repair of TOF is controversial. We hypothesize that TOF repair in the neonatal period is associated with worse outcomes compared with those who undergo repair later in infancy. We analyzed data using the Kids' Inpatient Database (KID) from 2003 to 2012. We used multivariable logistic regression analyses to compare the in-hospital outcomes between those who underwent total repair of TOF during the neonatal period vs the postneonatal period. There were 6,856 cases of TOF and 7.83% (n = 537) of those underwent repair during the neonatal period. The average mortality in all TOF repair was 2.1% (n = 147). In multiple regression model, compared with repair in postneonatal period, neonatal repair was associated with increased mortality, with adjusted odds ratio of 2.2 (95% confidence interval [CI]: 1.1 to 4.3, p = 0.023). Regarding complications, the neonatal group was associated with higher risk of acute renal failure (8.9% vs 2.3%, p <0.001), need for cardiac catheterization (18.6% vs 8.3%, p <0.001), and ECMO use (4.4% vs1.6%, p <0.001). There was no difference in the rates of arrhythmia, respiratory failure, pulmonary hypertension, or sudden cardiac arrest. Children who underwent repair in the neonatal period had longer hospital stay compared with the postneonatal group (45.5 days [95% CI: 39.3 to 51.7] vs 12.6 days [95% CI: 11.7 to 13.4], p <0.001). Hospital charges were higher for children who underwent repair in the neonatal period compared with those in the postneonatal period. In conclusion, TOF repair in the neonatal period is associated with higher rates of mortality, more postoperative complications, longer hospital stays, and higher hospitalization cost.

Acetazolamide fails to decrease pulmonary artery pressure at high altitude in partially acclimatized humans.

In this randomized, double-blind placebo controlled trial our objectives were to determine if acetazolamide is capable of preventing high altitude pulmonary edema (HAPE) in trekkers traveling between 4250 m (Pheriche)\4350 m (Dingboche) and 5000 m (Lobuje) in Nepal; to determine if acetazolamide decreases pulmonary artery systolic pressures (PASP) at high altitude; and to determine if there is an association with PASP and signs and symptoms of HAPE. Participants received either acetazolamide 250 mg PO BID or placebo at Pheriche\Dingboche and were reassessed in Lobuje. The Lake Louise Consensus Criteria were used for the diagnosis of HAPE, and cardiac ultrasonography was used to measure the velocity of tricuspid regurgitation and estimate PASP. Complete measurements were performed on 339 of the 364 subjects (164 in the placebo group, 175 in the acetazolamide group). No cases of HAPE were observed in either study group nor were differences in the signs and symptoms of HAPE found between the two groups. Mean PASP values did not differ significantly between the acetazolamide and placebo groups (31.3 and 32.6 mmHg, respectively). An increasing number of signs and symptoms of HAPE was associated with elevated PASP (p < 0.01). The efficacy of acetazolamide against acute mountain sickness, however, was significant with a 21.9% incidence in the placebo group compared to 10.2 % in the acetazolamide group (p < 0.01). Given the lack of cases of HAPE in either group, we can draw no conclusions about the efficacy of acetazolamide in preventing HAPE, but the absence of effect on PASP suggests that any effect may be minor possibly owing to partial acclimatization during the trek up to 4200 m.