The Association of Gestational Age and Size with Management Strategies and Outcomes in Symptomatic Neonatal Tetralogy of Fallot.

 In neonatal, symptomatic tetralogy of Fallot (sTOF), data are lacking on whether high-risk groups would benefit from staged (SR) or complete repair (CR). We studied the association of gestational age (GA) at birth and z-score for birth weight (BWz), with management strategy and outcomes in sTOF. California population-based cohort study (2011-2017) of infants with sTOF (defined as catheter or surgical intervention prior to 44 weeks corrected GA) was performed, comparing management strategy and timing by GA and BWz categories. Multivariable models evaluated composite outcomes and days alive and out of hospital (DAOOH) in the first year of life. Among 345 patients (SR = 194; CR = 151), management strategy did not differ by GA or BWz with complete repair defined as prior to 44 weeks corrected gestational age; however, did differ by GA with regard to complete/timely repair (defined as complete repair within first 30 days of life). Full-term and early-term neonates underwent CR 20 (95%CI: - 27.1, - 14.1; p < 0.001) and 15 days (95%CI: - 22.1, - 8.2; p < 0.001) sooner than preterm neonates. Prematurity and major anomaly were associated with mortality or non-cardiac morbidity, while only major anomaly was associated with mortality or cardiac morbidity (OR = 3.5, 95%CI: 1.8,6.7, p < .0001). Full-term infants had greater DAOOH compared to preterm infants (35.2 days, 95%CI: 4.0, 66.5, p = 0.03). LGA infants and those with major anomaly had significantly lower DAOOH. In sTOF, patient specific risk factors such as prematurity and major anomaly were more associated with outcomes than management strategy.

Mortality and Major Neonatal Morbidity in Preterm Infants with Serious Congenital Heart Disease.

OBJECTIVE: To investigate the trends of 1-year mortality and neonatal morbidities in preterm infants with serious congenital heart disease (CHD). STUDY DESIGN: This cohort study used a population-based administrative dataset of all liveborn infants of 26-36 weeks gestational age with serious CHD born in California between 2011 and 2017. We assessed 1-year mortality and major neonatal morbidities (ie, retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage grade >2, and periventricular leukomalacia) across the study period and compared these outcomes with those in infants without CHD. RESULTS: We identified 1921 preterm infants with serious CHD. The relative risk (RR) of death decreased by 10.6% for each year of the study period (RR, 0.89; 95% CI, 0.84-0.95), and the RR of major neonatal morbidity increased by 8.3% for each year (RR, 1.08; 95% CI, 1.02-1.15). Compared with preterm neonates without any CHD (n = 234 522), the adjusted risk difference (ARD) for mortality was highest at 32 weeks of gestational age (9.7%; 95% CI, 8.3%-11.2%), that for major neonatal morbidity was highest at 28 weeks (21.9%; 95% CI, 17.0%-26.9%), and that for the combined outcome was highest at 30 weeks (26.7%; 95% CI, 23.3%-30.1%). CONCLUSIONS: Mortality in preterm neonates with serious CHD decreased over the last decade, whereas major neonatal morbidities increased. Preterm infants with a gestational age of 28-32 weeks have the highest mortality or morbidity compared with their peers without CHD. These results support the need for specialized and focused medical neonatal care in preterm neonates with serious CHD.

Extracorporeal Membrane Oxygenation in Pediatric Pulmonary Hypertension.

OBJECTIVE: To describe the epidemiology, critical care interventions, and mortality of children with pulmonary hypertension receiving extracorporeal membrane oxygenation. DESIGN: Retrospective analysis of prospectively collected multicenter data. SETTING: Data entered into the Extracorporeal Life Support Organization database between January 2007 and November 2018. PATIENTS: Pediatric patients between 28 days and 18 years old with a diagnosis of pulmonary hypertension. MEASUREMENTS AND MAIN RESULTS: Six hundred thirty-four extracorporeal membrane oxygenation runs were identified (605 patients). Extracorporeal membrane oxygenation support type was pulmonary (43.1%), cardiac (40.2%), and extracorporeal cardiopulmonary resuscitation (16.7%). The majority of cannulations were venoarterial (80.4%), and 30% had a pre-extracorporeal membrane oxygenation cardiac arrest. Mortality in patients with pulmonary hypertension was 51.3% compared with 44.8% (p = 0.001) in those without pulmonary hypertension. In univariate analyses, significant predictors of mortality included age less than 6 months and greater than 5 years; pre-extracorporeal membrane oxygenation cardiac arrest; pre-extracorporeal membrane oxygenation blood gas with pH less than 7.12, PaCO2 greater than 75, PaO2 less than 35, and arterial oxygen saturation less than 60%; extracorporeal membrane oxygenation duration greater than 280 hours; extracorporeal cardiopulmonary resuscitation; and extracorporeal membrane oxygenation complications including cardiopulmonary resuscitation, inotropic support, myocardial stun, tamponade, pulmonary hemorrhage, intracranial hemorrhage, seizures, other hemorrhage, disseminated intravascular coagulation, renal replacement therapy, mechanical/circuit problem, and metabolic acidosis. A co-diagnosis of pneumonia was associated with significantly lower odds of mortality (odds ratio, 0.5; 95% CI, 0.3-0.8). Prediction models were developed using three sets of variables: 1) pre-extracorporeal membrane oxygenation (age, absence of pneumonia, and pH < 7.12; area under the curve, 0.62); 2) extracorporeal membrane oxygenation related (extracorporeal cardiopulmonary resuscitation, any neurologic complication, pulmonary hemorrhage, renal replacement therapy, and metabolic acidosis; area under the curve, 0.72); and 3) all variables combined (area under the curve, 0.75) (p < 0.001). CONCLUSIONS: Children with pulmonary hypertension who require extracorporeal membrane oxygenation support have a significantly greater odds of mortality compared with those without pulmonary hypertension. Risk factors for mortality include age, absence of pneumonia, pre-extracorporeal membrane oxygenation acidosis, extracorporeal cardiopulmonary resuscitation, pulmonary hemorrhage, neurologic complications, renal replacement therapy, and acidosis while on extracorporeal membrane oxygenation. Identification of those pulmonary hypertension patients requiring extracorporeal membrane oxygenation who are at even higher risk for mortality may inform clinical decision-making and improve prognostic awareness.

Initial presentation and management of pediatric heart failure.

PURPOSE OF REVIEW: Heart failure is a rare but morbid diagnosis in the pediatric patient presenting to the emergency department (ED). Familiarity of the ED physician with the presentation, work-up, and management of pediatric heart failure is essential as accurate diagnosis is reliant on a high degree of suspicion. RECENT FINDINGS: Studies evaluating pediatric heart failure are limited by its rarity and the heterogeneity of underlying conditions. However, recent reports have provided new data on the epidemiology, presentation, and outcomes of children with heart failure. SUMMARY: The recent studies reviewed here highlight the significant diagnostic and management challenges that pediatric heart failure presents given the variety and lack of specificity of its presenting signs, symptoms, and diagnostic work-up. This review provides the ED physician with a framework for understanding of pediatric heart failure to allow for efficient diagnosis and management of these patients. The primary focus of this review is heart failure in structurally normal hearts.

Factors Associated With Mortality in Children Who Successfully Wean From Extracorporeal Membrane Oxygenation.

OBJECTIVES: Extracorporeal membrane oxygenation is an established therapy for cardiac and respiratory failure unresponsive to usual care. Extracorporeal membrane oxygenation mortality remains high, with ongoing risk of death even after successful decannulation. We describe occurrence and factors associated with mortality in children weaned from extracorporeal membrane oxygenation. DESIGN: Retrospective cohort study. SETTING: Two hundred five extracorporeal membrane oxygenation centers reporting to the Extracorporeal Life Support Organization. SUBJECTS: Eleven thousand ninety-six patients, less than 18 years, supported with extracorporeal membrane oxygenation during 2007-2013, who achieved organ recovery before decannulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was hospital mortality less than or equal to 30 days post extracorporeal membrane oxygenation decannulation. Among 11,096 patients, indication for extracorporeal membrane oxygenation cannulation was respiratory (6,206; 56%), cardiac (3,663; 33%), or cardiac arrest (extracorporeal cardiopulmonary resuscitation, 1,227; 11%); the majority were supported with venoarterial extracorporeal membrane oxygenation at some stage in their course (8,576 patients; 77%). Mortality was 13%. Factors associated with mortality included younger age (all < 1 yr categories compared with older, p < 0.05), lower weight among neonates (≤ 3 vs > 3 kg; p < 0.001), mode of extracorporeal membrane oxygenation support (venoarterial extracorporeal membrane oxygenation compared with venovenous extracorporeal membrane oxygenation, p < 0.001), longer admission to extracorporeal membrane oxygenation cannulation time (≥ 28 vs < 28 hr; p < 0.001), cardiac and extracorporeal cardiopulmonary resuscitation compared with respiratory extracorporeal membrane oxygenation (both p < 0.001), extracorporeal membrane oxygenation duration greater than or equal to 135 hours (p < 0.001), preextracorporeal membrane oxygenation hypoxemia (PO2 ≤ 43 vs > 43 mm Hg; p < 0.001), preextracorporeal membrane oxygenation acidemia (p < 0.001), and extracorporeal membrane oxygenation complications, particularly cerebral or renal (both p < 0.001). CONCLUSIONS: Despite extracorporeal membrane oxygenation decannulation for organ recovery, 13% of patients die in hospital. Mortality is associated with patient factors, preextracorporeal membrane oxygenation illness severity, and extracorporeal membrane oxygenation management. Evidence-based strategies to optimize readiness for extracorporeal membrane oxygenation decannulation and postextracorporeal membrane oxygenation decannulation care are needed.

Intensive Care Mortality Prognostic Model for Pediatric Pulmonary Hypertension.

OBJECTIVES: The disease burden and mortality of children with pulmonary hypertension are significantly higher than for the general PICU population. We aimed to develop a risk-adjustment tool predicting PICU mortality for pediatric pulmonary hypertension patients: the Pediatric Index of Pulmonary Hypertension Intensive Care Mortality score. DESIGN: Retrospective analysis of prospectively collected multicenter pediatric critical care data. SETTING: One-hundred forty-three centers submitting data to Virtual Pediatric Systems database between January 1, 2009, and December 31, 2015. PATIENTS: Patients 21 years old or younger with a diagnosis of pulmonary hypertension. INTERVENTIONS: Twenty-one demographic, diagnostic, and physiologic variables obtained within 12 hours of PICU admission were assessed for inclusion. Multivariable logistic regression with stepwise selection was performed to develop the final model. Receiver operating characteristic curves were used to compare the Pediatric Index of Pulmonary Hypertension Intensive Care Mortality score with Pediatric Risk of Mortality 3 and Pediatric Index of Mortality 2 scores. MEASUREMENTS AND MAIN RESULTS: Fourteen-thousand two-hundred sixty-eight admissions with a diagnosis of pulmonary hypertension were included. Primary outcome was PICU mortality. Fourteen variables were selected for the final model: age, bradycardia, systolic hypotension, tachypnea, pH, FIO2, hemoglobin, blood urea nitrogen, creatinine, mechanical ventilation, nonelective admission, previous PICU admission, PICU admission due to nonsurgical cardiovascular disease, and cardiac arrest immediately prior to admission. The receiver operating characteristic curve for the Pediatric Index of Pulmonary Hypertension Intensive Care Mortality model (area under the curve = 0.77) performed significantly better than the receiver operating characteristic curves for Pediatric Risk of Mortality 3 (area under the curve = 0.71; p < 0.001) and Pediatric Index of Mortality 2 (area under the curve = 0.69; p < 0.001), respectively. CONCLUSIONS: The Pediatric Index of Pulmonary Hypertension Intensive Care Mortality score is a parsimonious model that performs better than Pediatric Risk of Mortality 3 and Pediatric Index of Mortality 2 for mortality in a multicenter cohort of pediatric pulmonary hypertension patients admitted to PICUs. Application of the Pediatric Index of Pulmonary Hypertension Intensive Care Mortality model to pulmonary hypertension patients in the PICU might facilitate earlier identification of patients at high risk for mortality and improve the ability to prognosticate for patients and families.

Stroke in Acquired and Congenital Heart Disease Patients and Its Relationship to Hospital Mortality and Lasting Neurologic Deficits.

OBJECTIVE: To describe strokes in patients with acquired or congenital heart disease and investigate risk factors for in-hospital mortality and ongoing neurologic deficits. DESIGN: Single-center, retrospective review of cardiac, neurologic, and radiologic patient databases. SETTING: Tertiary care children's hospital. PATIENTS: All patients with acquired or congenital heart disease admitted from January 2010 to October 2014 identified with stroke. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-four stroke events were identified in 83 patients (median age, 5.9 mo; interquartile range, 0.8-33.4). Thirty-two patients (38%) had single ventricle congenital heart disease. Eight patients (9%) presented with symptoms at home, and the remainder was diagnosed while already admitted to the hospital. Forty patients (48%) presented with clinically evident neurologic deficits (e.g., weakness, seizures). Fifty-eight patients (69%) had arterial ischemic strokes, and 13 (15%) had parenchymal hemorrhages. At diagnosis, 54 patients (64%) were on inotropes. Twenty-nine patients (35%) had greater than or equal to 3 cardiac procedures during their hospitalization before stroke diagnosis. In-hospital mortality occurred in 28 patients (33%). Under multivariate analysis, inotropes, number of cardiac procedures, lack of seizure, and parenchymal hemorrhage were independently associated with in-hospital mortality (p < 0.05). Fifty-four percent of survivors with neurologic follow-up had ongoing neurologic deficits attributable to strokes (median follow-up, 15.3 mo; interquartile range, 7.0-29.9). With multivariate analysis, longer hospital stay (p = 0.02) was independently associated with ongoing deficits. CONCLUSIONS: A majority of patients with acquired or congenital heart disease who suffer stroke present while hospitalized and without focal neurologic findings. In-hospital mortality is associated with inotropes, cardiac procedures, lack of seizure, and parenchymal hemorrhage. The majority of survivors have lasting neurologic deficits associated with longer hospital stay.

Extracorporeal membrane oxygenation for the support of adults with acute myocarditis.

OBJECTIVES: To characterize survival outcomes for adult patients with acute myocarditis supported with extracorporeal membrane oxygenation and identify risk factors for in-hospital mortality. DESIGN: Retrospective review of Extracorporeal Life Support Organization registry database. SETTING: Data reported to Extracorporeal Life Support Organization by 230 extracorporeal membrane oxygenation centers. PATIENTS: Patients 16 years old or older supported with extracorporeal membrane oxygenation for myocarditis during 1995 to 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 150 separate runs of extracorporeal membrane oxygenation for 147 patients with a diagnosis of acute myocarditis in the Extracorporeal Life Support Organization database from 1995 through 2011. Survival to hospital discharge was 61%. Nine patients underwent heart transplantation, and transplant-free survival to discharge was 56%. Extracorporeal membrane oxygenation was deployed during extracorporeal cardiopulmonary resuscitation in 31 patients (21% of the cohort). In a multivariate model evaluating pre-extracorporeal membrane oxygenation and extracorporeal membrane oxygenation support factors, pre-extracorporeal membrane oxygenation arrest (adjusted odds ratio, 2.4; 95% CI, 1.1-5.0) and need for higher extracorporeal membrane oxygenation flows at 4 hours post-extracorporeal membrane oxygenation cannulation (odds ratio, 2.8; 95% CI, 1.1-7.3) were associated with increased odds of in-hospital mortality. In a second multivariate model evaluating adverse events while on extracorporeal membrane oxygenation, central nervous system injury (odds ratio, 26.5; 95% CI, 7.3-96.6), renal failure (odds ratio, 3.6; 95% CI, 1.4-9.3), arrhythmia (odds ratio, 5.8; 95% CI, 2.2-15.1), and hyperbilirubinemia (odds ratio, 9.1; 95% CI, 2.6-31.8) were associated with increased odds of in-hospital mortality. CONCLUSIONS: Extracorporeal membrane oxygenation can be used effectively in adults with myocarditis to support the circulation while awaiting myocardial recovery. Early extracorporeal membrane oxygenation deployment prior to cardiac arrest may be associated with better outcomes.

Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart.

The heart is formed from cardiogenic progenitors expressing the transcription factors Nkx2-5 and Isl1 (refs 1 and 2). These multipotent progenitors give rise to cardiomyocyte, smooth muscle and endothelial cells, the major lineages of the mature heart. Here we identify a novel cardiogenic precursor marked by expression of the transcription factor Wt1 and located within the epicardium-an epithelial sheet overlying the heart. During normal murine heart development, a subset of these Wt1(+) precursors differentiated into fully functional cardiomyocytes. Wt1(+) proepicardial cells arose from progenitors that express Nkx2-5 and Isl1, suggesting that they share a developmental origin with multipotent Nkx2-5(+) and Isl1(+) progenitors. These results identify Wt1(+) epicardial cells as previously unrecognized cardiomyocyte progenitors, and lay the foundation for future efforts to harness the cardiogenic potential of these progenitors for cardiac regeneration and repair.

Extracorporeal membrane oxygenation-supported cardiopulmonary resuscitation following stage 1 palliation for hypoplastic left heart syndrome.

OBJECTIVES: To report on survival from a large multicenter cohort of neonates with hypoplastic left heart syndrome requiring extracorporeal membrane oxygenation-assisted cardiopulmonary resuscitation after stage 1 palliation operation. DESIGN: Retrospective analysis of data from the Extracorporeal Life Support Organization data registry (1998 through 2013). We computed the survival to hospital discharge for neonates (age < 30 d) who required extracorporeal membrane oxygenation after stage 1 palliation and evaluated factors associated with mortality using multivariate logistic regression analysis. SETTING: Multicenter data reported to Extracorporeal Life Support Organization registry. PATIENTS: Infants with hypoplastic left heart syndrome after stage 1 palliation who received extracorporeal membrane oxygenation-assisted cardiopulmonary resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 307 extracorporeal membrane oxygenation runs in the setting of extracorporeal membrane oxygenation-assisted cardiopulmonary resuscitation in 293 neonates with hypoplastic left heart syndrome following stage 1 palliation operation. The median age at cannulation was 9 days (interquartile range, 5-14 d). Survival to hospital discharge was 36%. In univariate analysis, gestational age, weight, extracorporeal membrane oxygenation duration, presence of air embolism, hemorrhagic complications, renal failure, and pulmonary complications (pulmonary hemorrhage and pneumothorax) were all associated with nonsurvival. In multivariate analysis, lower body weight at cannulation (odds ratio, 3.9; 95% CI, 1.9-8.3), duration of the extracorporeal membrane oxygenation (odds ratio, 3.4; 95% CI, 1.9-7.3), and renal failure while on extracorporeal membrane oxygenation (odds ratio, 2; 95% CI, 1.2-3.5) increased odds of mortality. CONCLUSIONS: Mortality for neonates with hypoplastic left heart syndrome supported with extracorporeal membrane oxygenation-assisted cardiopulmonary resuscitation after stage 1 palliation is high. Lower body weight, increased duration of extracorporeal membrane oxygenation support, and renal failure increased mortality.

Extracorporeal Membrane Oxygenation Cannulation Timing in the Pediatric Myocarditis Population: An Exploratory Analysis From the Extracorporeal Life Support Organization Registry.

Children presenting with acute myocarditis may experience rapid clinical deterioration requiring extracorporeal membrane oxygenation (ECMO); however, our understanding of best practices and timing of ECMO initiation are lacking. We explored the relationships between pre-cannulation factors and survival in this high-acuity patient population. DESIGN: Retrospective review of a large international registry. Primary outcome was survival to hospital discharge, stratified by incident cardiac arrest (CA) prior to ECMO and time to cannulation after intubation. SETTING AND SUBJECTS: The Extracorporeal Life Support Organization registry was queried for patients less than or equal to 18 years old receiving ECMO support for myocarditis between 2007 and 2018. Exclusion criteria included being nonindex runs, non-venoarterial ECMO or missing data points for main variables studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Population characteristics and survival were compared using t test, Wilcoxon rank-sum test, or Fisher exact test. Multivariable logistic regression was used for significant factors in the unadjusted logistic regression. Among 506 index ECMO runs in pediatric patients with myocarditis, survival for the cohort was 72%, with no difference between early and late eras (2007-2012 vs 2013-2018; p = 0.69). Survivors demonstrated higher pre-ECMO pH levels as well as shorter intubation-to-cannulation (ITC) times (3 hr [interquartile range (IQR)], 1-14 hr vs 6 hr [IQR, 2-20 hr]; p = 0.021). CA occurred within 24 hours prior to ECMO cannulation, including extracorporeal cardiopulmonary resuscitation, in 54% of ECMO runs (n = 273). Accounting for the interaction between pre-ECMO CA occurrence and ITC time, longer ITC time remained associated with lower survival for patients who did not experience a CA prior to ECMO, with adjusted odds ratio of 0.09 (IQR, 0.02-0.40; p = 0.002) for ITC time greater than or equal to 18 hours. CONCLUSIONS: The results of this multicenter analysis of ECMO utilization and outcomes for pediatric myocarditis suggest that patients approaching ECMO cannulation who have not experienced CA may have better survival outcomes if cannulated onto ECMO early after intubation.

Survival of neonates with enteroviral myocarditis requiring extracorporeal membrane oxygenation.

OBJECTIVES: Neonates infected with enteroviruses may present with severe myocarditis and medically refractory cardiopulmonary collapse. Extracorporeal membrane oxygenation (ECMO) has been used to support patients in this setting, but its efficacy has not been systematically studied. We sought to review the Extracorporeal Life Support Organization registry to determine survival rates and identify predictors of in hospital mortality for these neonates. DESIGN: Retrospective cohort study using data reported to the Extracorporeal Life Support Organization registry. SETTING: Multi-institutional data. PATIENTS: Patients ≤ 15 days old with enteroviral myocarditis who required ECMO support between 2000 and 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty-four neonates with enteroviral myocarditis were reported to the Extracorporeal Life Support Organization registry during the study period. The survival to hospital discharge rate was 33% (n = 8). Multisystem organ dysfunction was more common in nonsurvivors than in survivors (75% vs. 0%, p < .01). In particular, nonsurvivors had a higher prevalence of renal dysfunction (50% vs. 0%, p = .02). Nonsurvivors also had a greater number of ECMO-related complications (5 vs. 3.5, p = .03). CONCLUSIONS: Cardiopulmonary support with ECMO should be considered for neonates with severe enteroviral myocarditis that fails conventional medical therapies. Multisystem organ dysfunction, particularly with renal involvement, may portend a poor prognosis and is one of several factors that should be considered in the decision to initiate and/or continue mechanical support for these patients.

Perioperative factors associated with prolonged mechanical ventilation after complex congenital heart surgery.

OBJECTIVE: To evaluate perioperative factors associated with prolonged mechanical ventilation in children undergoing complex cardiac surgery for congenital heart disease. DESIGN: Retrospective chart review. SETTING: A tertiary care pediatric cardiac intensive care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This retrospective cohort study included all patients undergoing complex cardiac surgical procedures (Risk Adjustment in Congenital Heart Surgery-1 category ≥ 3) at our institution during 2003. We defined prolonged mechanical ventilation as need for mechanical ventilation for ≥ 7 days (90th percentile of duration of mechanical ventilation for the whole cohort). Multivariate logistic regression analyses were used to determine independent relationships between perioperative factors and prolonged mechanical ventilation. A total of 362 patients were admitted to the cardiac intensive care unit after a cardiac surgical procedure of Risk Adjustment in Congenital Heart Surgery-1 ≥ 3 level of complexity and survived to hospital discharge. Median age was 242 days (range, 4 days-14.4 yrs), the median duration of mechanical ventilation was 1.5 days (range, 0-7 days), and 41 patients (11%) were ventilated for ≥ 7 days. Age of <30 days at surgery, higher Pediatric Risk of Mortality III score at the time of cardiac intensive care unit admission, the presence of major noncardiac structural anomalies, healthcare-associated infections, noninfectious pulmonary complications (pleural effusions and pneumothorax), and the need for reintervention were all independently associated with prolonged mechanical ventilation. CONCLUSIONS: Younger age, greater severity of illness at postoperative admission, healthcare-associated infections, noninfectious pulmonary complications, and the need for reintervention are associated with prolonged mechanical ventilation after complex cardiac surgery. Future studies and quality improvement initiatives should focus on those risk factors that are modifiable to promote early extubation in children recovering from complex congenital heart surgery.

Perioperative care of children with tetralogy of fallot.

OPINION STATEMENT: Complete surgical repair of tetralogy of Fallot (TOF) around 3 months of age is the commonly undertaken management strategy in many centers and has excellent outcomes. Intervention at an earlier age, including the newborn period, may be required for children with symptoms. Early extubation from mechanical ventilation where possible may help improve outcomes for children undergoing complete repair of TOF.

Congenital Cardiothoracic Surgeons and Palliative Care: A National Survey Study.

BACKGROUND: The majority of children with advanced heart disease in the inpatient setting die in an intensive care unit under 1 year of age following multiple interventions. While pediatric cardiology and palliative care provider attitudes have been described, little is known about pediatric cardiothoracic surgeon attitudes toward palliative care in children with advanced heart disease. OBJECTIVE: To describe perspectives of pediatric cardiothoracic surgeons regarding palliative care in pediatric heart disease. DESIGN: Cross-sectional web-based national survey. RESULTS: Of the 220 surgeons who were e-mailed the survey, 36 opened the survey and 5 did not meet inclusion criteria (n = 31). Median years of practice was 23.5 (range: 12-41 years), and 87.1% were male. Almost all (90%) reported that they had experience consulting palliative care. While 68% felt palliative care consultation was initiated at the appropriate time, 29% felt it occurred too late. When asked the appropriate timing for palliative care consultation in hypoplastic left heart syndrome, 45% selected "at time of prenatal diagnosis" and 30% selected "when surgical and transcatheter options have been exhausted." Common barriers to palliative care involvement included the perception of "giving up" (40%) and concern for undermining parental hope (36%). CONCLUSIONS: While a majority of pediatric cardiothoracic surgeons are familiar with palliative care, there is variation in perception of appropriate timing of consultation. Significant barriers to consultation still exist, including concern that parents will think they are "giving" up, undermining parental hope, and influence of palliative care on the medical care team's approach.

Association between Z-score for birth weight and postoperative outcomes in neonates and infants with congenital heart disease.

OBJECTIVE: We hypothesized that infants with fetal growth restrictions have increased mortality and morbidity after congenital heart disease surgery. METHODS: The study included patients in The Society of Thoracic Surgeons Congenital Heart Surgery Database (2010-2016) who underwent cardiac surgery at a corrected gestational age of ≤44 weeks. Patients were classified as severely (birth weight Z-score -4 to -2), moderately (Z-score -2 to -1), and mildly growth restricted (Z-score -1.0 to -0.5) and compared with a reference population (Z-score 0-0.5). Multivariable logistic regression clustering on center was used to evaluate the association of birth weight Z-score with operative mortality and postoperative complications and its interaction with gestational age was assessed. RESULTS: In 25,244 patients, operative mortality was 8.6% and major complications occurred in 19.4%. Compared with the reference group, the adjusted odds ratio (AOR) of mortality was increased in infants with severe (AOR, 2.4; 95% confidence interval [CI], 2.0-3.0), moderate (AOR, 1.7; 95% CI, 1.4-2.0), and mild growth restriction (AOR, 1.4; 95% CI, 1.2-1.6). The AOR for major postoperative complications was increased for severe (AOR, 1.4; 95% CI, 1.2-1.7) and moderate growth restriction (AOR, 1.2; 95% CI, 1.1-1.4). There was significant interaction between birth weight Z-score and gestational age (P = .007). CONCLUSIONS: Even birth weight Z-scores slightly below average are independent risk factors for mortality and morbidity in infants who undergo cardiac surgery. The strongest association between poor fetal growth and operative mortality exists in early-term infants. These novel findings might account for some of the previously unexplained variation in cardiac surgical outcomes.

Extracorporeal membrane oxygenation for the support of infants, children, and young adults with acute myocarditis: a review of the Extracorporeal Life Support Organization registry.

OBJECTIVE: To describe survival outcomes for pediatric patients supported with extracorporeal membrane oxygenation for severe myocarditis and identify risk factors for in-hospital mortality. DESIGN: Retrospective review of Extracorporeal Life Support Organization registry database. SETTING: Data reported to Extracorporeal Life Support Organization from 116 extracorporeal membrane oxygenation centers. PATIENTS: Patients < or = 18 yrs of age supported with extracorporeal membrane oxygenation for myocarditis during 1995 to 2006. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 19,348 reported pediatric extracorporeal membrane oxygenation uses from 1995 to 2006, 260 runs were for 255 patients with a diagnosis of myocarditis (1.3%). Survival to hospital discharge was 61%. Seven patients (3%) underwent heart transplantation and six patients survived to discharge. Of 100 patients not surviving to hospital discharge, extracorporeal membrane oxygenation support was withdrawn in 70 (70%) with multiple organ failure as the indication in 58 (83%) patients. In a multivariable model, female gender (adjusted odds ratio, 2.3, 95% confidence interval, 1.3-4.2), arrhythmia on extracorporeal membrane oxygenation (adjusted odds ratio, 2.7, 95% confidence interval, 1.5-5.1), and renal failure requiring dialysis (adjusted odds ratio, 5.1, 95% confidence interval, 2.3-11.4) were associated with increased odds of in-hospital mortality. CONCLUSION: Extracorporeal membrane oxygenation is a valuable tool to rescue children with severe cardiorespiratory compromise related to myocarditis. Female gender, arrhythmia on extracorporeal membrane oxygenation, and need for dialysis during extracorporeal membrane oxygenation were associated with increased mortality.

Environmental and Socioeconomic Factors Influence the Live-Born Incidence of Congenital Heart Disease: A Population-Based Study in California.

BACKGROUND The development of congenital heart disease (CHD) is multifactorial with genetic and environmental influences. We sought to determine the relationship between socioeconomic and environmental factors with the incidence of CHD among live-born infants in California and to determine whether maternal comorbidities are in the causal pathway. METHODS AND RESULTS This was a population-based cohort study in California (2007-2012). The primary outcome was having significant CHD. Predictors included socioeconomic status and environmental exposure to pollutants determined by U.S. Census data. A social deprivation index and environmental exposure index was assigned based on neighborhood socioeconomic variables, categorized into 4 quartiles. Quartile 1 was the best with the least exposure to pollutants and social deprivation, and quartile 4 was the worst. Multivariate logistic regression and mediation analyses were performed. Among 2 419 651 live-born infants, the incidence of CHD was 3.2 per 1000 live births. The incidence of CHD was significantly higher among those in quartile 4 compared with quartile 1 (social deprivation index: 0.35% versus 0.29%; odds ratio [OR], 1.31; 95% CI, 1.21-1.41; environmental exposure index: 0.35% versus 0.29%; OR, 1.23; 95% CI, 1.15-1.31) after adjusting for maternal race/ethnicity and age and accounting for the relationship between the 2 primary predictors. Maternal comorbidities explained 13% (95% CI, 10%-20%) of the relationship between social deprivation index and environmental exposure index with the incidence of CHD. CONCLUSIONS Increased social deprivation and exposure to environmental pollutants are associated with the incidence of live-born CHD in California. Maternal comorbidities explain some, but not all, of this relationship. These findings identify targets for social policy initiatives to minimize health disparities.

Gata4 is essential for the maintenance of jejunal-ileal identities in the adult mouse small intestine.

Gata4, a member of the zinc finger family of GATA transcription factors, is highly expressed in duodenum and jejunum but is nearly undetectable in distal ileum of adult mice. We show here that the caudal reduction of Gata4 is conserved in humans. To test the hypothesis that the regional expression of Gata4 is critical for the maintenance of jejunal-ileal homeostasis in the adult small intestine in vivo, we established an inducible, intestine-specific model that results in the synthesis of a transcriptionally inactive Gata4 mutant. Synthesis of mutant Gata4 in jejuna of 6- to 8-week-old mice resulted in an attenuation of absorptive enterocyte genes normally expressed in jejunum but not in ileum, including those for the anticipated targets liver fatty acid binding protein (Fabp1) and lactase-phlorizin hydrolase (LPH), and a surprising induction of genes normally silent in jejunum but highly expressed in ileum, specifically those involved in bile acid transport. Inactivation of Gata4 resulted in an increase in the goblet cell population and a redistribution of the enteroendocrine subpopulations, all toward an ileal phenotype. The gene encoding Math1, a known activator of the secretory cell fate, was induced approximately 75% (P < 0.05). Gata4 is thus an important positional signal required for the maintenance of jejunal-ileal identities in the adult mouse small intestine.