Methylprednisolone for Heart Surgery in Infants - A Randomized, Controlled Trial.

BACKGROUND: Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown. METHODS: We conducted a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (<1 year of age) undergoing heart surgery with cardiopulmonary bypass at 24 sites participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Registry data were used in the evaluation of outcomes. The infants were randomly assigned to receive prophylactic methylprednisolone (30 mg per kilogram of body weight) or placebo, which was administered into the cardiopulmonary-bypass pump-priming fluid. The primary end point was a ranked composite of death, heart transplantation, or any of 13 major complications. Patients without any of these events were assigned a ranked outcome based on postoperative length of stay. In the primary analysis, the ranked outcomes were compared between the trial groups with the use of odds ratios adjusted for prespecified risk factors. Secondary analyses included an unadjusted odds ratio, a win ratio, and safety outcomes. RESULTS: A total of 1263 infants underwent randomization, of whom 1200 received either methylprednisolone (599 infants) or placebo (601 infants). The likelihood of a worse outcome did not differ significantly between the methylprednisolone group and the placebo group (adjusted odds ratio, 0.86; 95% confidence interval [CI], 0.71 to 1.05; P = 0.14). Secondary analyses (unadjusted for risk factors) showed an odds ratio for a worse outcome of 0.82 (95% CI, 0.67 to 1.00) and a win ratio of 1.15 (95% CI, 1.00 to 1.32) in the methylprednisolone group as compared with the placebo group, findings suggestive of a benefit with methylprednisolone; however, patients in the methylprednisolone group were more likely than those in the placebo group to receive postoperative insulin for hyperglycemia (19.0% vs. 6.7%, P<0.001). CONCLUSIONS: Among infants undergoing surgery with cardiopulmonary bypass, prophylactic use of methylprednisolone did not significantly reduce the likelihood of a worse outcome in an adjusted analysis and was associated with postoperative development of hyperglycemia warranting insulin in a higher percentage of infants than placebo. (Funded by the National Center for Advancing Translational Sciences and others; STRESS ClinicalTrials.gov number, NCT03229538.).

National Variation in Congenital Heart Surgery Outcomes.

BACKGROUND: Optimal strategies to improve national congenital heart surgery outcomes and reduce variability across hospitals remain unclear. Many policy and quality improvement efforts have focused primarily on higher-risk patients and mortality alone. Improving our understanding of both morbidity and mortality and current variation across the spectrum of complexity would better inform future efforts. METHODS: Hospitals participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database (2014-2017) were included. Case mix-adjusted operative mortality, major complications, and postoperative length of stay were evaluated using Bayesian models. Hospital variation was quantified by the interdecile ratio (IDR, upper versus lower 10%) and 95% credible intervals (CrIs). Stratified analyses were performed by risk group (Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery [STAT] category) and simulations evaluated the potential impact of reductions in variation. RESULTS: A total of 102 hospitals (n=84 407) were included, representing ≈85% of US congenital heart programs. STAT category 1 to 3 (lower risk) operations comprised 74% of cases. All outcomes varied significantly across hospitals: adjusted mortality by 3-fold (upper versus lower decile 5.0% versus 1.6%, IDR 3.1 [95% CrI 2.5-3.7]), mean length of stay by 1.8-fold (19.2 versus 10.5 days, IDR 1.8 [95% CrI 1.8-1.9]), and major complications by >3-fold (23.5% versus 7.0%, IDR 3.4 [95% CrI 3.0-3.8]). The degree of variation was similar or greater for low- versus high-risk cases across outcomes, eg, ≈3-fold mortality variation across hospitals for STAT 1 to 3 (IDR 3.0 [95% CrI 2.1-4.2]) and STAT 4 or 5 (IDR 3.1 [95% CrI 2.4-3.9]) cases. High-volume hospitals had less variability across outcomes and risk categories. Simulations suggested potential reductions in deaths (n=282), major complications (n=1539), and length of stay (101 183 days) over the 4-year study period if all hospitals were to perform at the current median or better, with 37% to 60% of the improvement related to the STAT 1 to 3 (lower risk) group across outcomes. CONCLUSIONS: We demonstrate significant hospital variation in morbidity and mortality after congenital heart surgery. Contrary to traditional thinking, a substantial portion of potential improvements that could be realized on a national scale were related to variability among lower-risk cases. These findings suggest modifications to our current approaches to optimize care and outcomes in this population are needed.

Postoperative Hematocrit and Adverse Outcomes in Pediatric Cardiac Surgery Patients: A Cross-Sectional Study From the Society of Thoracic Surgeons and Congenital Cardiac Anesthesia Society Database Collaboration.

BACKGROUND: We sought to examine potential associations between pediatric postcardiac surgical hematocrit values and postoperative complications or mortality. METHODS: A retrospective, cross-sectional study from the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) and Congenital Cardiac Anesthesia Society Database Module (2014-2019) was completed. Multivariable logistic regression models, adjusting for covariates in the STS-CHSD mortality risk model, were used to assess the relationship between postoperative hematocrit and the primary outcomes of operative mortality or any major complication. Hematocrit was assessed as a continuous variable using linear splines to account for nonlinear relationships with outcomes. Operations after which the oxygen saturation is typically observed to be <92% were classified as cyanotic and ≥92% as acyanotic. RESULTS: In total, 27,462 index operations were included, with 4909 (17.9%) being cyanotic and 22,553 (82.1%) acyanotic. For cyanotic patients, each 5% incremental increase in hematocrit over 42% was associated with a 1.31-fold (95% confidence interval [CI], 1.10-1.55; P = .003) increase in the odds of operative mortality and a 1.22-fold (95% CI, 1.10-1.36; P < .001) increase in the odds of a major complication. For acyanotic patients, each 5% incremental increase in hematocrit >38% was associated with a 1.45-fold (95% CI, 1.28-1.65; P < .001) increase in the odds of operative mortality and a 1.21-fold (95% CI, 1.14-1.29; P < .001) increase in the odds of a major complication. CONCLUSIONS: High hematocrit on arrival to the intensive care unit (ICU) is associated with increased operative mortality and major complications in pediatric patients following cardiac surgery.

Improving the prediction of long-term readmission and mortality using a novel biomarker panel.

OBJECTIVE: Several short-term readmission and mortality prediction models have been developed using clinical risk factors or biomarkers among patients undergoing coronary artery bypass graft (CABG) surgery. The use of biomarkers for long-term prediction of readmission and mortality is less well understood. Given the established association of cardiac biomarkers with short-term adverse outcomes, we hypothesized that 5-year prediction of readmission or mortality may be significantly improved using cardiac biomarkers. MATERIALS AND METHODS: Plasma biomarkers from 1149 patients discharged alive after isolated CABG surgery from eight medical centers were measured in a cohort from the Northern New England Cardiovascular Disease Study Group between 2004 and 2007. We assessed the added predictive value of a biomarker panel with a clinical model against the clinical model alone and compared the model discrimination using the area under the receiver operating characteristic (AUROC) curves. RESULTS: In our cohort, 461 (40%) patients were readmitted or died within 5 years. Long-term outcomes were predicted by applying the STS ASCERT clinical model with an AUROC of 0.69. The biomarker panel with the clinical model resulted in a significantly improved AUROC of 0.74 (p value <.0001). Across 5 years, the hazard ratio for patients in the second to fifth quintile predicted probabilities from the biomarker augmented STS ASCERT model ranged from 2.2 to 7.9 (p values <.001). CONCLUSIONS: We report that a panel of biomarkers significantly improved prediction of long-term readmission or mortality risk following CABG surgery. Our findings suggest biomarkers help clinical care teams better assess the long-term risk of readmission or mortality.

Associations between anthropometric indices and outcomes of congenital heart operations in infants and young children: An analysis of data from the Society of Thoracic Surgeons Database.

BACKGROUND: Children with congenital heart disease are at risk for growth failure due to inadequate nutrient intake and increased metabolic demands. We examined the relationship between anthropometric indices of nutrition (height-for-age z-score [HAZ], weight-for-age z-score [WAZ], weight-for-height z-score [WHZ]) and outcomes in a large sample of children undergoing surgery for congenital heart disease. METHODS: Patients in the Society of Thoracic Surgeons Congenital Heart Surgery Database having index cardiac surgery at age 1 month to 10 years were included. Indices were calculated by comparing patients' weight and height to population norms from the World Health Organization and Centers for Disease Control and Prevention. Outcomes included operative mortality, composite mortality or major complication, major postoperative infection, and postoperative length of stay. For each outcome and index, the adjusted odds ratio (aOR) (for mortality, composite outcome, and infection) and adjusted relative change in median (for postoperative length of stay) for a 1-unit decrease in index were estimated using mixed-effects logistic and log-linear regression models. RESULTS: Every unit decrease in HAZ was associated with 1.40 aOR of mortality (95% CI 1.32-1.48), and every unit decrease in WAZ was associated with 1.33 aOR for mortality (95% CI 1.25-1.41). The relationship between WHZ and outcome was nonlinear, with aOR of mortality of 0.84 (95% CI 0.76-0.93) for 1-unit decrease when WHZ ≥ 0 and a nonsignificant association for WHZ < 0. Trends for other outcomes were similar. Overall, the incidence of low nutritional indices was similar for 1-ventricle and 2-ventricle patients. Children between the age of 1 month and 1 year and those with lesions associated with pulmonary overcirculation had the highest incidence of low nutritional indices. CONCLUSIONS: Lower HAZ and WAZ, suggestive of malnutrition, are associated with increased mortality and other adverse outcomes after cardiac surgery in infants and young children. Higher WHZ over zero, suggestive of obesity, is also associated with adverse outcomes.

Overcoming underpowering: Trial simulations and a global rank end point to optimize clinical trials in children with heart disease.

BACKGROUND: Randomized controlled trials (RCTs) in children with heart disease are challenging and therefore infrequently performed. We sought to improve feasibility of perioperative RCTs for this patient cohort using data from a large, multicenter clinical registry. We evaluated potential enrollment and end point frequencies for various inclusion cohorts and developed a novel global rank trial end point. We then performed trial simulations to evaluate power gains with the global rank end point and with use of planned covariate adjustment as an analytic strategy. METHODS: Data from the Society of Thoracic Surgery-Congenital Heart Surgery Database (STS-CHSD, 2011-2016) were used to support development of a consensus-based global rank end point and for trial simulations. For Monte Carlo trial simulations (n = 50,000/outcome), we varied the odds of outcomes for treatment versus placebo and evaluated power based on the proportion of trial data sets with a significant outcome (P < .05). RESULTS: The STS-CHSD study cohort included 35,967 infant index cardiopulmonary bypass operations from 103 STS-CHSD centers, including 11,411 (32%) neonatal cases and 12,243 (34%) high-complexity (Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery mortality category ≥4) cases. In trial simulations, study power was 21% for a mortality-only end point, 47% for a morbidity and mortality composite, and 78% for the global rank end point. With covariate adjustment, power increased to 94%. Planned covariate adjustment was preferable to restricting to higher-risk cohorts despite higher event rates in these cohorts. CONCLUSIONS: Trial simulations can inform trial design. Our findings, including the newly developed global rank end point, may be informative for future perioperative trials in children with heart disease.

Rationale and design of the STeroids to REduce Systemic inflammation after infant heart Surgery (STRESS) trial.

For decades, physicians have administered corticosteroids in the perioperative period to infants undergoing heart surgery with cardiopulmonary bypass (CPB) to reduce the postoperative systemic inflammatory response to CPB. Some question this practice because steroid efficacy has not been conclusively demonstrated and because some studies indicate that steroids could have harmful effects. STRESS is a randomized, placebo-controlled, double-blind, multicenter trial designed to evaluate safety and efficacy of perioperative steroids in infants (age < 1 year) undergoing heart surgery with CPB. Participants (planned enrollment = 1,200) are randomized 1:1 to methylprednisolone (30 mg/kg) administered into the CPB pump prime versus placebo. The trial is nested within the existing infrastructure of the Society of Thoracic Surgeons Congenital Heart Surgery Database. The primary outcome is a global rank score of mortality, major morbidities, and hospital length of stay with components ranked commensurate with their clinical severity. Secondary outcomes include several measures of major postoperative morbidity, postoperative hospital length of stay, and steroid-related safety outcomes including prevalence of hyperglycemia and postoperative infectious complications. STRESS will be one of the largest trials ever conducted in children with heart disease and will answer a decades-old question related to safety and efficacy of perioperative steroids in infants undergoing heart surgery with CPB. The pragmatic "trial within a registry" design may provide a mechanism for conducting low-cost, high-efficiency trials in a heretofore-understudied patient population.

Registry-based trials: a potential model for cost savings?

BACKGROUND/AIMS: Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials. METHODS: We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design. RESULTS: Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field. CONCLUSIONS: Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.

A Study of Practice Behavior for Endotracheal Intubation Site for Children With Congenital Heart Disease Undergoing Surgery: Impact of Endotracheal Intubation Site on Perioperative Outcomes-An Analysis of the Society of Thoracic Surgeons Congenital Cardiac Anesthesia Society Database.

BACKGROUND: In adults undergoing cardiopulmonary bypass surgery, oral intubation is typically preferred over nasal intubation due to reduced risk of sinusitis and infection. In children, nasal intubation is more common and sometimes preferred due to perceived benefits of less postoperative sedation and a lower risk for accidental extubation. This study sought to describe the practice of nasal intubation in the pediatric population undergoing cardiopulmonary bypass surgery and assess the risks/benefits of a nasal route against an oral one. METHODS: Patients <18 years of age in the Society of Thoracic Surgeons Congenital Heart Surgery Database between January 2010 and December 2015 were included. Patients with a preoperative endotracheal tube, tracheostomy, or known airway anomalies were excluded. Multivariable modeling was used to assess the association between route of tracheal intubation and a composite measure of infection risk (wound infection, mediastinitis, septicemia, pneumonia, and endocarditis). Covariates were included to adjust for important patient characteristics (eg, weight, age, comorbidities), case complexity, and center effects. Secondary outcomes included length of intubation, hospital length of stay, and airway complications including accidental extubations. We also performed a subanalysis in children <12 months of age in high-volume centers (>100 cases/y) examining how infection risk may change with age at the time of surgery. RESULTS: Nasal intubation was used in 41% of operations in neonates, 38% in infants, 15% in school-aged children, and 2% in adolescents. Nasal intubation appeared protective for accidental extubation only in neonates (P = .02). Multivariable analysis in infants and neonates showed that the nasal route of intubation was not associated with the infection composite (relative risk [RR], 0.84; 95% CI, 0.59-1.18) or a shorter length of stay (RR, 0.992; 95% CI, 0.947-1.039), but was associated with a shorter intubation length (RR, 0.929; 95% CI, 0.869-0.992). Restricting to high-volume centers showed a significant interaction between age and intubation route with a risk change for infection occurring between approximately 6-12 months of age (P = .003). CONCLUSIONS: While older children undergoing nasal intubation trend similar to the adult population with an increased risk of infection, nasal intubation in neonates and infants does not appear to carry a similar risk. Nasal intubation in neonates and infants may also be associated with a shorter intubation length but not a shorter length of stay. Prospective studies are required to better understand these complex associations.

Biomarkers associated with 30-day readmission and mortality after pediatric congenital heart surgery.

OBJECTIVES: Novel cardiac biomarkers serum (suppression of tumorigenicity [ST2]) and Galectin-3 may be associated with an increased likelihood of important events after cardiac surgery. Our objective was to explore the association between pre- and postoperative serum biomarker levels and 30-day readmission or mortality for pediatric patients. METHODS: We prospectively enrolled pediatric patients <18 years of age who underwent at least one cardiac surgical operation at Johns Hopkins Children's Center from 2010 to 2014 (N = 162). Blood samples were collected immediately before surgery and at the end of bypass. We evaluated the association between pre- and postoperative Galectin-3 and ST2 with 30-day readmission or mortality, using backward stepwise logistic regression, adjusting for covariates based on the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Mortality Risk Model. RESULTS: In our cohort, 21 (12.9%) patients experienced readmission or mortality 30-days from discharge. Before adjustment, preoperative ST2 terciles demonstrated a strong association with readmission and/or mortality after surgery (OR: 2.58; 95% CI: 1.17-3.66 and OR: 4.37; 95% CI: 1.31-14.57). After adjustment for covariates based on the STS congenital risk model, Galectin-3 postoperative mid-tercile was significantly associated with 30-day readmission or mortality (OR: 6.17; 95% CI: 1.50-0.43) as was the highest tercile of postoperative ST2 (OR: 4.98; 95% CI: 1.06-23.32). CONCLUSIONS: Elevated pre-and postoperative levels of ST2 and Galectin-3 are associated with increased risk of readmission or mortality after pediatric heart surgery. These clinically available biomarkers can be used for improved risk stratification and may guide improved patient care management.

Prenatal Diagnosis Influences Preoperative Status in Neonates with Congenital Heart Disease: An Analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database.

The early postnatal course for a newborn with critical congenital heart disease (CHD) can be negatively impacted if diagnosis is delayed. Despite this, there continues to be inconsistent evidence regarding potential benefits associated with prenatal diagnosis (PND) in neonates who undergo cardiac surgery. The objective of this study was to better define the impact of a PND on pre-operative morbidity by utilizing a large clinical database. Neonates (< 30 days) undergoing heart surgery from 2010 to 2014 and entered in the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) were included. Multivariable logistic regression was used to evaluate the association between PND and a composite measure including nine major pre-operative risk factors. Co-variates were included to adjust for important patient characteristics (e.g., weight-for-age z-score, genetic syndromes, prematurity), case complexity, and center effects. Centers and patients with excess missing data for relevant co-variates were excluded. Included were 12,899 neonates undergoing surgery at 112 centers. Major pre-operative risk factors were present in 34% overall. By univariate analysis, PND was associated with a lower overall prevalence of major pre-operative risk factors. After adjusting for potential confounders, major pre-operative risk factors were less prevalent among neonates with PND compared to neonates without PND (adjusted OR 0.62, 95% CI 0.57-0.68, p < 0.001). A sensitivity analysis excluding neonates with genetic syndromes, non-cardiac anatomic abnormalities, and prematurity demonstrated similar findings (adjusted OR 0.55, 95% CI 0.49-0.61, p < 0.0001). Among neonates with CHD, prenatal diagnosis is associated with significantly lower rates of pre-operative risk factors for cardiac surgery. Further studies are needed to define association of these pre-operative benefits of a PND with longer term clinical outcomes.

Biomarkers improve prediction of 30-day unplanned readmission or mortality after paediatric congenital heart surgery.

OBJECTIVE: To evaluate the association between novel pre- and post-operative biomarker levels and 30-day unplanned readmission or mortality after paediatric congenital heart surgery. METHODS: Children aged 18 years or younger undergoing congenital heart surgery (n = 162) at Johns Hopkins Hospital from 2010 to 2014 were enrolled in the prospective cohort. Collected novel pre- and post-operative biomarkers include soluble suppression of tumorgenicity 2, galectin-3, N-terminal prohormone of brain natriuretic peptide, and glial fibrillary acidic protein. A model based on clinical variables from the Society of Thoracic Surgery database was developed and evaluated against two augmented models. RESULTS: Unplanned readmission or mortality within 30 days of cardiac surgery occurred among 21 (13%) children. The clinical model augmented with pre-operative biomarkers demonstrated a statistically significant improvement over the clinical model alone with a receiver-operating characteristics curve of 0.754 (95% confidence interval: 0.65-0.86) compared to 0.617 (95% confidence interval: 0.47-0.76; p-value: 0.012). The clinical model augmented with pre- and post-operative biomarkers demonstrated a significant improvement over the clinical model alone, with a receiver-operating characteristics curve of 0.802 (95% confidence interval: 0.72-0.89; p-value: 0.003). CONCLUSIONS: Novel biomarkers add significant predictive value when assessing the likelihood of unplanned readmission or mortality after paediatric congenital heart surgery. Further exploration of the utility of these novel biomarkers during the pre- or post-operative period to identify early risk of mortality or readmission will aid in determining the clinical utility and application of these biomarkers into routine risk assessment.

Lessons learned in the use of clinical registry data in a multi-centre prospective study: the Pediatric Heart Network Residual Lesion Score Study.

BACKGROUND: Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology. OBJECTIVES: We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders' perspectives, and provide recommendations to guide future studies using this methodology. METHODS: The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff. RESULTS: Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes. CONCLUSIONS: Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.

Effect of Obesity and Underweight Status on Perioperative Outcomes of Congenital Heart Operations in Children, Adolescents, and Young Adults: An Analysis of Data From the Society of Thoracic Surgeons Database.

BACKGROUND: Extreme body mass index (BMI; either very high or very low) has been associated with increased risk of adverse perioperative outcome in adults undergoing cardiac surgery. The effect of BMI on perioperative outcomes in congenital heart disease patients has not been evaluated. METHODS: A multicenter retrospective cohort study was performed studying patients 10 to 35 years of age undergoing a congenital heart disease operation in the Society of Thoracic Surgeons Congenital Heart Surgery Database between January 1, 2010, and December 31, 2015. The primary outcomes were operative mortality and a composite outcome (1 or more of operative mortality, major adverse event, prolonged hospital length of stay, and wound infection/dehiscence). The associations between age- and sex-adjusted BMI percentiles and these outcomes were assessed, with adjustment for patient-level risk factors, with multivariate logistic regression. RESULTS: Of 18 337 patients (118 centers), 16% were obese, 15% were overweight, 53% were normal weight, 7% were underweight, and 9% were severely underweight. Observed risks of operative mortality (P=0.04) and composite outcome (P<0.0001) were higher in severely underweight and obese subjects. Severely underweight BMI was associated with increased unplanned cardiac operation and reoperation for bleeding. Obesity was associated with increased risk of wound infection. In multivariable analysis, the association between BMI and operative mortality was no longer significant. Obese (odds ratio, 1.28; P=0.008), severely underweight (odds ratio, 1.29; P<0.0001), and underweight (odds ratio, 1.39; P=0.002) subjects were associated with increased risk of composite outcome. CONCLUSIONS: Obesity and underweight BMI were associated with increased risk of composite adverse outcome independently of other risk factors. Further research is necessary to determine whether BMI represents a modifiable risk factor for perioperative outcome.

Risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or therapeutic cardiac catheterisation.

BACKGROUND: Paediatric hospital-associated venous thromboembolism is a leading quality and safety concern at children's hospitals. OBJECTIVE: The aim of this study was to determine risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or therapeutic cardiac catheterisation. METHODS: We conducted a retrospective, case-control study of children admitted to the cardiovascular intensive care unit at Johns Hopkins All Children's Hospital (St. Petersburg, Florida, United States of America) from 2006 to 2013. Hospital-associated venous thromboembolism cases were identified based on ICD-9 discharge codes and validated using radiological record review. We randomly selected two contemporaneous cardiovascular intensive care unit controls without hospital-associated venous thromboembolism for each hospital-associated venous thromboembolism case, and limited the study population to patients who had undergone cardiothoracic surgery or therapeutic cardiac catheterisation. Odds ratios and 95% confidence intervals for associations between putative risk factors and hospital-associated venous thromboembolism were determined using univariate and multivariate logistic regression. RESULTS: Among 2718 admissions to the cardiovascular intensive care unit during the study period, 65 met the criteria for hospital-associated venous thromboembolism (occurrence rate, 2%). Restriction to cases and controls having undergone the procedures of interest yielded a final study population of 57 hospital-associated venous thromboembolism cases and 76 controls. In a multiple logistic regression model, major infection (odds ratio=5.77, 95% confidence interval=1.06-31.4), age ⩽1 year (odds ratio=6.75, 95% confidence interval=1.13-160), and central venous catheterisation (odds ratio=7.36, 95% confidence interval=1.13-47.8) were found to be statistically significant independent risk factors for hospital-associated venous thromboembolism in these children. Patients with all three factors had a markedly increased post-test probability of having hospital-associated venous thromboembolism. CONCLUSION: Major infection, infancy, and central venous catheterisation are independent risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or cardiac catheter-based intervention, which, in combination, define a high-risk group for hospital-associated venous thromboembolism.

Transfer of Neonates with Critical Congenital Heart Disease Within a Regionalized Network.

Regionalization of pediatric cardiac surgical care varies between and within states. In most geographic regions, at least some neonates with critical heart disease are transferred from their birth hospital to a different hospital for surgery. The impact of neonatal transfer for surgery, particularly over a considerable distance (>10 miles), has been largely unexplored. We sought to examine the impact of transferring neonates for cardiac surgery. We queried the New York State Cardiac Surgery database (2005-2014) from a single institution to identify neonates born within the cardiac surgery center and those transferred for surgery. Outcomes were compared between groups, with subgroup analysis of neonates with single ventricle anatomy. 113 surgical neonates were born at the cardiac surgery center, and 268 were transferred to the cardiac surgery center. Median transfer distance was 91 (IQR 73, 94) miles. Age at operation and the need for preoperative ventilation were significantly lower in neonates born at the cardiac surgery center. In addition, single ventricle anatomy was more prevalent among those born at the cardiac surgery center (48.7 vs. 31.3%; p = 0.001). However, postoperative outcomes were the same-30-day survival was similar across groups (birth: 89% vs. transfer: 90%; p = 0.7), and for those with single ventricle palliation (birth: 81% vs. transfer: 81%; p = 0.9). Within our regionalized network, we found no difference in 30-day survival between neonates either born or transferred to a cardiac surgery center, which supports the use of a regionalized network of hospitals to the care of children with congenital heart disease.

Nomenclature for congenital and paediatric cardiac disease: the International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Iteration of the International Classification of Diseases (ICD-11).

An internationally approved and globally used classification scheme for the diagnosis of CHD has long been sought. The International Paediatric and Congenital Cardiac Code (IPCCC), which was produced and has been maintained by the International Society for Nomenclature of Paediatric and Congenital Heart Disease (the International Nomenclature Society), is used widely, but has spawned many "short list" versions that differ in content depending on the user. Thus, efforts to have a uniform identification of patients with CHD using a single up-to-date and coordinated nomenclature system continue to be thwarted, even if a common nomenclature has been used as a basis for composing various "short lists". In an attempt to solve this problem, the International Nomenclature Society has linked its efforts with those of the World Health Organization to obtain a globally accepted nomenclature tree for CHD within the 11th iteration of the International Classification of Diseases (ICD-11). The International Nomenclature Society has submitted a hierarchical nomenclature tree for CHD to the World Health Organization that is expected to serve increasingly as the "short list" for all communities interested in coding for congenital cardiology. This article reviews the history of the International Classification of Diseases and of the IPCCC, and outlines the process used in developing the ICD-11 congenital cardiac disease diagnostic list and the definitions for each term on the list. An overview of the content of the congenital heart anomaly section of the Foundation Component of ICD-11, published herein in its entirety, is also included. Future plans for the International Nomenclature Society include linking again with the World Health Organization to tackle procedural nomenclature as it relates to cardiac malformations. By doing so, the Society will continue its role in standardising nomenclature for CHD across the globe, thereby promoting research and better outcomes for fetuses, children, and adults with congenital heart anomalies.

Abnormalities in serum biomarkers correlate with lower cardiac index in the Fontan population.

BACKGROUND: Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients. Methods and results This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman's Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6-33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (-0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (-0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63-0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)]. CONCLUSIONS: Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.

Outcomes Following Single and Recurrent In-Hospital Cardiac Arrests in Children With Heart Disease: A Report From American Heart Association's Get With the Guidelines Registry-Resuscitation.

OBJECTIVES: Little is known regarding patient characteristics and outcomes associated with cardiac arrest in hospitalized children with underlying heart disease. We described clinical characteristics and in-hospital outcomes in cardiac patients with both single and recurrent cardiac arrests. DESIGN: Retrospective analysis evaluating characteristics and outcomes in single versus recurrent arrest groups in unadjusted and adjusted analyses. SETTING: American Heart Association's Get with the Guidelines-Resuscitation registry (2000-2010). PATIENTS: Children younger than 18 years, identified with medical or surgical cardiac disease and one or more in-hospital cardiac arrest. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: One thousand eight hundred and eighty-nine patients with 2,387 cardiac arrests from 157 centers met inclusion criteria: 1,546 (82%) with a single arrest and 343 (18%) with a recurrent arrest. More than two thirds of recurrent cardiac arrests occurred in ICUs, and those with recurrent arrest had a higher prevalence of baseline comorbidities (e.g., more likely to be mechanically ventilated and receiving vasoactive infusions). Overall survival to hospital discharge was 51%, and was lower in the recurrent versus single arrest group (41% vs 53%; p < 0.001). In analysis adjusted for baseline comorbidities, there was no longer a statistically significant association between recurrent arrest and survival (odds ratio, 0.74; 95% CI, 0.33-1.63; p = 0.45). In stratified analysis, the relationship between recurrent arrest and lower survival was more prominent in the surgical-cardiac (odds ratio, 0.39; 95% CI, 0.14-1.11; p = 0.09) versus medical-cardiac (odds ratio, 0.96; 95% CI, 0.28-3.30; p = 0.95) group. CONCLUSIONS: In this large multicenter study, half of pediatric cardiac patients who suffered a cardiac arrest survived to hospital discharge. Lower survival in the group with recurrent arrest may be explained in part by the higher prevalence of baseline comorbidities in these patients, and surgical cardiac patients appeared to be at greatest risk. Further study is necessary to develop strategies to reduce subsequent mortality in these high-risk patients.

Gestational age at birth and outcomes after neonatal cardiac surgery: an analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database.

BACKGROUND: Gestational age at birth is a potentially important modifiable risk factor in neonates with congenital heart disease. We evaluated the relationship between gestational age and outcomes in a multicenter cohort of neonates undergoing cardiac surgery, focusing on those born at early term (ie, 37-38 weeks' gestation). METHODS AND RESULTS: Neonates in the Society of Thoracic Surgeons Congenital Heart Surgery Database who underwent cardiac surgery between 2010 and 2011 were included. Multivariable logistic regression was used to evaluate the association of gestational age at birth with in-hospital mortality, postoperative length of stay, and complications, adjusting for other important patient characteristics. Of 4784 included neonates (92 hospitals), 48% were born before 39 weeks' gestation, including 31% at 37 to 38 weeks. Compared with a 39.5-week gestational age reference level, birth at 37 weeks' gestational age was associated with higher in-hospital mortality, with an adjusted odds ratio (95% confidence interval) of 1.34 (1.05-1.71; P=0.02). Complication rates were higher and postoperative length of stay was significantly prolonged for those born at 37 and 38 weeks' gestation (adjusted P<0.01 for all). Late-preterm births (34-36 weeks' gestation) also had greater mortality and postoperative length of stay (adjusted P≤0.003 for all). CONCLUSIONS: Birth during the early term period of 37 to 38 weeks' gestation is associated with worse outcomes after neonatal cardiac surgery. These data challenge the commonly held perception that delivery at any time during term gestation is equally safe and appropriate and question the related practice of elective delivery of fetuses with complex congenital heart disease at early term.