Intrahepatic Transcriptomics Differentiate Advanced Fibrosis and Clinical Outcomes in Adults With Fontan Circulation.

BACKGROUND: The molecular mechanisms underlying Fontan-associated liver disease (FALD) remain largely unknown. OBJECTIVES: This study aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. METHODS: This retrospective cohort study included adults with the Fontan circulation. Baseline clinical, laboratory, imaging, and hemodynamic data as well as a composite clinical outcome (CCO) were extracted from medical records. Patients were classified into early or advanced fibrosis. RNA was isolated from formalin-fixed paraffin-embedded liver biopsy samples; RNA libraries were constructed with the use of an rRNA depletion method and sequenced on an Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were performed with the use of DESeq2 and Metascape. RESULTS: A total of 106 patients (48% male, median age 31 years [IQR: 11.3 years]) were included. Those with advanced fibrosis had higher B-type natriuretic peptide levels and Fontan, mean pulmonary artery, and capillary wedge pressures. The CCO was present in 23 patients (22%) and was not predicted by advanced liver fibrosis, right ventricular morphology, presence of aortopulmonary collaterals, or Fontan pressures on multivariable analysis. Samples with advanced fibrosis had 228 upregulated genes compared with early fibrosis. Samples with the CCO had 894 upregulated genes compared with those without the CCO. A total of 136 upregulated genes were identified in both comparisons and were enriched in cellular response to cytokine stimulus or oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-ß signaling pathway, and vasculature development. CONCLUSIONS: Patients with FALD and advanced fibrosis or the CCO exhibited upregulated genes related to inflammation, congestion, and angiogenesis.

Fetal Pericardial Teratoma: Perinatal Management and Example of Preterm Cesarean Birth to Resection.

A very large fetal pericardial teratoma was diagnosed at 28 weeks' gestation, prompting urgent multidisciplinary expert consultations to weigh the risks and benefits of various prenatal invasive procedures and preterm delivery for postnatal surgical management. Ultimately, the infant was born by planned cesarean section and underwent immediate cardiopulmonary bypass and surgical resection.

Comparing apples to apples: Exploring public reporting of congenital cardiac surgery outcomes based on common congenital heart operations.

OBJECTIVE: We sought to simplify reporting of outcomes in congenital heart surgery that compares well-defined patient groups and accommodates multiple stakeholder needs while being easily understandable. METHODS: We selected 19 commonly performed congenital heart surgeries ranging in complexity from repair of atrial septal defects to the Norwood procedure. Strict inclusion/exclusion criteria ensured the creation of 19 well-defined diagnosis/procedure cohorts. Preoperative, procedural, and postoperative data were collected for consecutive eligible patients from 9 centers between January 1, 2016, and December 31, 2021. Unadjusted operative mortality rates and hospital length of stay for each of the 19 diagnosis/procedure cohorts were summarized in aggregate and stratified by each center. RESULTS: Of 8572 eligible cases included, numbers in the 19 diagnosis/procedure cohorts ranged from 73 for tetralogy of Fallot repair after previous palliation to 1224 for ventricular septal defect (VSD) repair for isolated VSD. In aggregate, the unadjusted mortality ranged from 0% for atrial septal defect repair to 28.4% for hybrid stage I. There was significant heterogeneity in case mix and mortality for different diagnosis/procedure cohorts across centers (eg, arterial switch operation/VSD, n = 7-42, mortality 0%-7.4%; Norwood procedure, n = 16-122, mortality 5.3%-25%). CONCLUSIONS: Reporting of institutional case volumes and outcomes within well-defined diagnosis/procedure cohorts can enable centers to benchmark outcomes, understand trends in mortality, and direct quality improvement. When made public, this type of report could provide parents with information on institutional volumes and outcomes and allow them to better understand the experience of each program with operations for specific congenital heart defects.

Whole-Exome Sequencing Identifies Homozygote Nonsense Variants in LMOD2 Gene Causing Infantile Dilated Cardiomyopathy.

As an essential component of the sarcomere, actin thin filament stems from the Z-disk extend toward the middle of the sarcomere and overlaps with myosin thick filaments. Elongation of the cardiac thin filament is essential for normal sarcomere maturation and heart function. This process is regulated by the actin-binding proteins Leiomodins (LMODs), among which LMOD2 has recently been identified as a key regulator of thin filament elongation to reach a mature length. Few reports have implicated homozygous loss of function variants of LMOD2 in neonatal dilated cardiomyopathy (DCM) associated with thin filament shortening. We present the fifth case of DCM due to biallelic variants in the LMOD2 gene and the second case with the c.1193G>A (p.W398*) nonsense variant identified by whole-exome sequencing. The proband is a 4-month male infant of Hispanic descent with advanced heart failure. Consistent with previous reports, a myocardial biopsy exhibited remarkably short thin filaments. However, compared to other cases of identical or similar biallelic variants, the patient presented here has an unusually late onset of cardiomyopathy during infancy. Herein, we present the phenotypic and histological features of this variant, confirm the pathogenic impact on protein expression and sarcomere structure, and discuss the current knowledge of LMOD2-related cardiomyopathy.

The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: Management of infants and neonates with tetralogy of Fallot.

OBJECTIVE: Despite decades of experience, aspects of the management of tetralogy of Fallot with pulmonary stenosis (TOF) remain controversial. Practitioners must consider newer, evolving treatment strategies with limited data to guide decision making. Therefore, the TOF Clinical Practice Standards Committee was commissioned by the American Association for Thoracic Surgery to provide a framework on this topic, focused on timing and types of interventions, management of high-risk patients, technical considerations during interventions, and best practices for assessment of outcomes of the interventions. In addition, the group was tasked with identifying pertinent research questions for future investigations. It is recognized that variability in institutional experience could influence the application of this framework to clinical practice. METHODS: The TOF Clinical Practice Standards Committee is a multinational, multidisciplinary group of cardiologists and surgeons with expertise in TOF. With the assistance of a medical librarian, a citation search in PubMed, Embase, Scopus, and Web of Science was performed using key words related to TOF and its management; the search was restricted to the English language and the year 2000 or later. Articles pertaining to pulmonary atresia, absent pulmonary valve, atrioventricular septal defects, and adult patients with TOF were excluded, as well as nonprimary sources such as review articles. This yielded nearly 20,000 results, of which 163 were included. Greater consideration was given to more recent studies, larger studies, and those using comparison groups with randomization or propensity score matching. Expert consensus statements with class of recommendation and level of evidence were developed using a modified Delphi method, requiring 80% of the member votes with 75% agreement on each statement. RESULTS: In asymptomatic infants, complete surgical correction between age 3 and 6 months is reasonable to reduce the length of stay, rate of adverse events, and need for a transannular patch. In the majority of symptomatic neonates, both palliation and primary complete surgical correction are useful treatment options. It is reasonable to consider those with low birth weight or prematurity, small or discontinuous pulmonary arteries, chromosomal anomalies, other congenital anomalies, or other comorbidities such as intracranial hemorrhage, sepsis, or other end-organ compromise as high-risk patients. In these high-risk patients, palliation may be preferred; and, in patients with amenable anatomy, catheter-based procedures may prove favorable over surgical palliation. CONCLUSIONS: Ongoing research will provide further insight into the role of catheter-based interventions. For complete surgical correction, both transatrial and transventricular approaches are effective; however, the smallest possible ventriculotomy should be utilized. When possible, the pulmonary valve should be spared; and if unsalvageable, reconstruction can be considered. At the conclusion of the operation, adequate relief of the right ventricular outflow obstruction should be confirmed, and identification of a significant fixed anatomical obstruction should prompt further intervention. Given our current knowledge and the gaps identified, we propose several key questions to be answered by future research and potentially by a TOF registry: When to palliate or proceed with complete surgical correction, as well as the ideal type of palliation; the optimal surgical approach for complete repair for the best long-term preservation of right ventricular function; and the utility, efficacy, and durability of various pulmonary valve preservation and reconstruction techniques.

Branch pulmonary artery stenosis after arterial switch operation: The effect of preoperative anatomic factors on reintervention.

BACKGROUND: We hypothesized that preoperative patient characteristics and branch pulmonary artery (PA) size might influence the rate of postoperative branch PA reintervention in patients with transposition of the great arteries who undergo the arterial switch operation (ASO). METHODS: The retrospective single-center study included 262 consecutive (2008-2017) newborns who underwent the ASO. Demographic characteristics, echocardiography, and clinical outcomes were reviewed. Competing risk analysis modeled incidence of branch PA reintervention and cause-specific hazard regression for predictors analyses. RESULTS: Median age and weight were 7 (range, 5-11) days and 3.4 (range, 3.1-3.8) kg, respectively. Various types of early branch PA reinterventions (concomitant revision or reintervention during the intensive care unit stay) were required in 28 (10.7%) patients. These patients had prolonged ventilation (P < .001), intensive care unit duration (P < .001), worse right ventricular function (P = .043), and high in-hospital mortality (P = .010). Branch PA dimensions significantly decreased immediately after ASO compared with baseline measurements. The median follow-up duration was 20.8 (range, 0.9-44.7) months. Branch PA reintervention was common among survivors without early reinterventions (9.4%), and even more frequent among those with early reinterventions (25%). Subsequent reintervention (all catheter-based) was necessary for more than one-third of patients after initial branch PA reintervention. The multivariable analysis showed preoperative dimension of the left PA (hazard ratio, 0.527 [95% CI, 0.337-0.823]; P = .005), and right PA (hazard ratio, 0.503 [95% CI, 0.318-0.796]; P = .003) were independently associated with late branch PA reinterventions. CONCLUSIONS: Branch PA reintervention was common and often required surgical or catheter-based reinterventions after ASO. PA branch diameters became significantly smaller after ASO. Smaller preoperative branch PA predicted late branch PA reintervention, indicating a smaller margin of geometrical tolerance to this effect.

3D Modeling and Printing in Congenital Heart Surgery: Entering the Stage of Maturation.

3D printing allows the most realistic perception of the surgical anatomy of congenital heart diseases without the requirement of physical devices such as a computer screen or virtual headset. It is useful for surgical decision making and simulation, hands-on surgical training (HOST) and cardiovascular morphology teaching. 3D-printed models allow easy understanding of surgical morphology and preoperative surgical simulation. The most common indications for its clinical use include complex forms of double outlet right ventricle and transposition of the great arteries, anomalous systemic and pulmonary venous connections, and heterotaxy. Its utility in congenital heart surgery is indisputable, although it is hard to "scientifically" prove the impact of its use in surgery because of many confounding factors that contribute to the surgical outcome. 3D-printed models are valuable resources for morphology teaching. Educational models can be produced for almost all different variations of congenital heart diseases, and replicated in any number. HOST using 3D-printed models enables efficient education of surgeons in-training. Implementation of the HOST courses in congenital heart surgical training programs is not an option but an absolute necessity. In conclusion, 3D printing is entering the stage of maturation in its use for congenital heart surgery. It is now time for imagers and surgeons to find how to effectively utilize 3D printing and how to improve the quality of the products for improved patient outcomes and impact of education and training.

Can We Still Improve Survival Outcomes of Neonatal Biventricular Repairs?

BACKGROUND: We sought to identify modifiable factors to improve survival of neonatal biventricular repair by analyzing the cause of death and predictors of mortality and reintervention in the last 2 decades. METHODS: Between 1995 and 2016, 991 consecutive neonates were included. The cohort was divided by era: era I was from 1995 to 1999, era II 2000 to 2007, and era III 2008 to 2016. The Kaplan-Meier method was used to estimate freedom from death and reintervention. Univariable and multivariable Cox regression was applied to assess predictors for mortality or reintervention in the contemporary cohorts (2000-2016). RESULTS: Median age was 8 days (range, 5-13), and median body weight at operation was 3.3 kg (range, 2.9-3.6). The most common diagnosis was transposition with intact ventricular septum (32%), followed by transposition with ventricular septal defect (14.5%), and simple left-to-right shunt lesion (10.9%). There was significant improvement in survival from era I to eras II and III but no difference between eras II and III (1 year: 82.1% vs 89.4% vs 89.6%, respectively; P < .001). The most common cause of death was sudden death in eras I and III and cardiac in era II. Multivariable analysis revealed preoperative (P = .005)/postoperative (P < .001) extracorporeal membrane oxygenation and postoperative renal replacement (P < .001) as independent predictors for mortality. The reintervention rates were comparable between eras II and III (P = .53). Atrioventricular septal defects and common atrial trunk were identified as predictors for reintervention. CONCLUSIONS: Survival after neonatal biventricular repair remained unchanged. Preventing sudden death, myocardial protection, and minimizing residual lesions are potential targets to improve outcomes.

Assessment tool validation and technical skill improvement in the simulation of the Norwood operation using three-dimensional-printed heart models.

OBJECTIVES: The hands-on surgical training course utilizes 3-dimensional (3D)-printed heart models to simulate complex congenital heart operations. This study aimed to validate a model and assessment tool in the simulation of 2 techniques of the Norwood operation and investigate whether technical performance improves following rehearsal with or without proctor presence. METHODS: Five 'experienced' and 5 'junior' surgeons performed 2 techniques of the Norwood operation on 3D-printed models of hypoplastic left heart syndrome. Performances were retrospectively assessed by 10 raters with varying experience in congenital heart surgery (CHS) (Medical Doctorate versus non-Medical Doctorate). Assessments were made with the procedure-specific Hands-On Surgical Training-CHS tool. Results were analysed for technical performance and rater consistency. Following validation, 30 surgeons (24 with proctor guidance and 6 with training videos and objective feedback only) simulated the Norwood operation twice. RESULTS: Performance scores were consistently higher for experienced surgeons and raters discriminated clearly between the experienced and junior surgeons (P ≤ 0.001). The hands-on surgical training-CHS tool showed high inter-rater (0.86) and intra-rater (0.80) reliability among all raters. Scores for both experienced and junior surgeons were highly consistent across all raters, with no statistically significant difference (P = 0.50). All surgeons successfully performed the Norwood operation. Sixty attempts were scored in total. Eighty-seven percentage (26/30) of surgeons' scores (mean: attempt 1 = 92, attempt 2 = 104) and times [mean: attempt 1 = 1:22:00, attempt 2 = 1:08:00 (h:mm:ss)] improved between the 2 attempts by 9% and 15% respectively (P ≤ 0.001). Total scores of all surgeons in the non-proctored subgroup (6) improved by 15% on average (mean: attempt 1 = 86, attempt 2 = 105, P = 0.002). CONCLUSIONS: Procedure-specific assessment tools can be developed to evaluate technical performance for complex CHS simulation and be performed reliably by non-expert raters. Rehearsal both under supervision and independently leads to technical skill improvement further supporting its value in CHS training.

Low preoperative superior vena cava blood flow predicts bidirectional cavopulmonary shunt failure.

BACKGROUND: In this study we sought to determine whether preoperative superior vena cava (SVC) blood flow measured using cardiac magnetic resonance (CMR) predicts physiology and clinical outcome after bidirectional cavopulmonary shunt (BCPS). METHODS: The retrospective single-center study included 65 (2012-2017) patients who underwent BCPS. Preoperative CMR imaging, echocardiography, catheterization, and clinical outcomes were reviewed. SVC flow was measured using phase contrast CMR. The Kaplan-Meier method and Cox regression was used for BCPS takedown-free survival and predictor analyses. RESULTS: The absolute and indexed SVC flow was 0.5 (interquartile range [IQR], 0.4-0.7) L/min and 1.7 (IQR, 1.4-2.0) L/min/mm2 respectively, which was comparable with the SVC blood flow volume previously measured. The median age and body weight at BCPS was 6.5 (IQR, 5.5-8.5) months and 6.9 (IQR, 6.0-7.7) kg. After follow-up, at a median of 17.1 (IQR, 7.9-41.3) months, 14 patients (21.5%) underwent the Fontan completion and 40 (61.5%) with BCPS physiology were waiting for the Fontan completion. The 11 remaining patients (16.9%), included those who underwent takedown (n = 7; 10.8%) or died with a BCPS (n = 4; 6.2%). Severe hypoxia was the leading cause of mortality, directly accounting for two-thirds of deaths (66.6%; 6/9). The BCPS takedown-free survival was 96.8% at 6 months, and 79.9% at 3 years. Preoperative SVC blood flow was significantly positively correlated with early post-BCPS arterial saturation (P = .00). The multivariable analysis showed SVC flow was the only factor associated with BCPS failure (hazard ratio, 0.186; P = .04) among the predictors related to the pre-BCPS anatomy and physiology. CONCLUSIONS: SVC blood flow might be as critically important as pulmonary artery anatomic and physiologic parameters in the evaluation of BCPS candidacy in the single-ventricle population.

Rapid Advancement in Enteral Nutrition Does Not Affect Systemic Inflammation and Insulin Homeostasis Following Pediatric Cardiopulmonary Bypass Surgery.

OBJECTIVES: To determine impact of enteral nutrition delivery on the relationship among inflammation, insulin resistance, and outcomes following pediatric cardiopulmonary bypass surgery. DESIGN: Pilot, randomized study analyzed according to intention-to-treat analysis. SETTING: Pediatric cardiac ICU. PATIENTS: Infants (≤ 6 mo) undergoing cardiopulmonary bypass. INTERVENTIONS: Patients randomly assigned to receive rapid escalation to enteral nutrition reaching goal feeds by 27 hours or standard feeding practice reaching goal feeds by 63 hours. Feeds were initiated on the first postoperative day. MEASUREMENTS AND MAIN RESULTS: Fifty patients were randomized equally to study arms. Patients were a median (interquartile range) of 16 days old (7-110 d old), undergoing biventricular surgery (88%) with a median cardiopulmonary bypass time of 125 minutes (105-159 min). Serial blood samples were drawn before and after cardiopulmonary bypass, cardiac ICU admission, and every 12 hours (up to 96 hr) for glucose, insulin, and cytokines (interleukin-1α, interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α) levels. Glucose-insulin ratio was calculated to quantify insulin resistance. Patient characteristics, time to enteral nutrition initiation, enteral nutrition interruptions, and insulin administration were similar across intervention arms. FF reached goal feeds at similar intervals as standard feeding (39 hr [30-60 hr] vs 60 hr [21-78 hr]; p = 0.75). No difference in cytokine, insulin, or glucose-insulin ratio was noted between groups. Higher inflammation was associated with increased glucose-insulin ratio and higher risk of adverse events. In multivariable models of interleukin-8, FF was associated with increased glucose-insulin ratio (estimate of effect [95% CI], 0.152 [0.033-0.272]; p = 0.013). Although higher interleukin-8 was associated with an elevated risk of adverse event, this relationship was possibly mitigated by FF (odds ratio [95% CI], 0.086 [0.002-1.638]; p = 0.13). CONCLUSIONS: A FF strategy was not associated with changes to early enteral nutrition delivery. Inflammation, insulin resistance, and morbidity were similar, but FF may modify the relationship between inflammation and adverse event. Multicenter nutrition studies are possible and necessary in this vulnerable population.

Development and validation of a procedure-specific assessment tool for hands-on surgical training in congenital heart surgery.

BACKGROUND: Hands-on surgical simulation has been sought to address training limitations within congenital heart surgery (CHS). However, there is a need for objective assessment methods to measure surgeons' performance to justify its global adoption. This study aimed to validate a procedure-specific assessment tool for the simulation of the arterial switch operation on 3D-printed models and to evaluate the consistency of scoring among evaluators with different levels of experience in CHS. METHODS: Five "expert" and 5 "junior" surgeons performed the arterial switch procedure on 3D-printed models with transposition of the great arteries during 2 hands-on surgical training courses. Their performance was retrospectively assessed by 9 evaluators with varying experience in CHS (staff surgeons, resident surgeons, and non-MD raters). Assessments were done using 2 assessment tools: the Hands-On Surgical Training-Congenital Heart Surgery (HOST-CHS) assessment tool and the global rating scale (GRS). RESULTS: The HOST-CHS tool showed a higher interrater and intrarater reliability compared with the GRS. Total scores for expert surgeons were highly consistent across all evaluators. Non-MD raters' total scores for junior surgeons were slightly higher than those of residents and staff evaluators. All grades of evaluator were able to discriminate between junior and expert surgeons. CONCLUSIONS: This study demonstrates the development and validation of an objective, procedure-specific assessment tool for the arterial switch operation with consistency among evaluators with different experience. There is now a platform for quantifying and accurately evaluating performance, which will be highly beneficial in training and developing the next generation of congenital heart surgeons.

Ppp1r1b-lncRNA inhibits PRC2 at myogenic regulatory genes to promote cardiac and skeletal muscle development in mouse and human.

Long noncoding RNAs (lncRNAs) have emerged as critical epigenetic regulators and play important roles in cardiac development and congenital heart disease. In a previous study, we identified a novel lncRNA, Ppp1r1b, with expression highly correlated with myogenesis. However, the molecular mechanism that underlies Ppp1r1b-lncRNA function in myogenic regulation is unknown. By silencing Ppp1r1b-lncRNA, mouse C2C12 and human skeletal myoblasts failed to develop fully differentiated myotubes. Myogenic differentiation was also impaired in PPP1R1B-lncRNA deficient human-induced pluripotent stem cell-derived cardiomyocytes (hiPSCs-CMs). The expression of myogenic transcription factors, including MyoD, Myogenin, and Tbx5, as well as sarcomere proteins, was significantly suppressed in Ppp1r1b-lncRNA inhibited myoblast cells and neonatal mouse heart. Histone modification analysis revealed increased H3K27 tri-methylation at MyoD1 and Myogenin promoters in GapmeR treated C2C12 cells. Furthermore, Ppp1r1b-lncRNA was found to bind to Ezh2, and chromatin isolation by RNA purification (ChIRP) assay revealed enriched interaction of Ppp1r1b-lncRNA with Myod1 and Tbx5 promoters, suggesting that Ppp1r1b-lncRNA induces transcription of myogenic transcription factors by interacting with the polycomb repressive complex 2 (PRC2) at the chromatin interface. Correspondingly, the silencing of Ppp1r1b-lncRNA increased EZH2 binding at promoter regions of myogenic transcription factors. Therefore, our results suggest that Ppp1r1b-lncRNA promotes myogenic differentiation through competing for PRC2 binding with chromatin of myogenic master regulators during heart and skeletal muscle development.

Quantitative assessment of technical performance during hands-on surgical training of the arterial switch operation using 3-dimensional printed heart models.

OBJECTIVE: Data supporting the use of hands-on simulation in congenital heart surgery are promising but primarily qualitative. This study aimed to demonstrate if there was an objective improvement in time and technical performance of the arterial switch procedure on 3-dimensional printed heart models by surgeons using a validated assessment method. METHODS: A total of 30 surgeons of varying experience performed the arterial switch procedure twice on 3-dimensional printed models with transposition of the great arteries during the Hands-on Surgical Training courses. Surgeons' performances were recorded and retrospectively assessed for both time and performance using the Hands-on Surgical Training-Congenital Heart Surgery tool, a validated procedure-specific assessment tool for the arterial switch. RESULTS: A total of 60 videos were scored. Eighty percent of surgeons (24/30) had improved from their first attempt. The mean total score of the first attempt performance compared with the second was 103 and 120, respectively, with a mean difference in score of 17 (95% confidence interval, 10-24). All surgeons were statistically significantly quicker in their second attempt. The mean time for the first attempt compared with the second was 1 hour, 28 minutes, 4 seconds and 1 hour, 5 minutes, and 45 seconds, respectively, with a mean difference of 0 hours, 22 minutes, 19 seconds (95% confidence interval, 0 hours, 15 minutes, 22 seconds to 0 hours, 25 minutes, 34 seconds). CONCLUSIONS: This is the first study to demonstrate an objective improvement in time and technical performance of the arterial switch procedure on 3-dimensional printed heart models. This supports the evidence that simulation in the form of deliberate practice with constructive, objective feedback is fundamental in the training of future congenital heart surgeons. These simulations and assessments should be incorporated to create structured, standardized training curricula within congenital heart surgery.

Feeding May Modulate the Relationship Between Systemic Inflammation, Insulin Resistance, and Poor Outcome Following Cardiopulmonary Bypass for Pediatric Cardiac Surgery.

BACKGROUND: Hyperglycemia is common following cardiopulmonary bypass (CPB) surgery and is associated with poor outcomes, often attributed to hyperinsulinemia and an acquired state of insulin resistance. This study examined the underpinnings of hyperglycemia and the effects of nutrition on the association with inflammation and clinical outcomes. METHODS: This prospective, observational cohort study enrolled consecutive children (<18 years) undergoing CPB. Serial measurements of inflammatory cytokines, glucose, insulin, and nutrition delivery were obtained. Glucose-insulin ratio (G:I) was calculated for each time point as a measure of insulin resistance (lower G:I reflects higher resistance). Clinical outcomes were recorded using a composite morbidity score. RESULTS: The 200 subjects studied were predominantly females (58%) undergoing biventricular repair (85%) at a median (interquartile range) age of 0.58 years (0.28, 3.4) and weight of 7.0 kg (3.1, 59.5). Hyperglycemia was common (49% of patients), coinciding with peak cytokine concentrations. Insulin levels were highest and G:I lowest immediately following separation from CPB but had no consistent relationship with cytokines. The morbidity outcome was reached by 23% of patients, with increased odds associated with higher interleukin (IL)6 and IL8 levels but not by glucose, insulin, or G:I. Providing higher feeding volumes attenuated this association between inflammation and morbidity. Higher feeds were not associated with G:I but appeared to decrease the strength of the relationship between cytokines and glycemic indices. CONCLUSION: Postoperative morbidity is independently associated with increased inflammation but not with hyperglycemia or markers of insulin resistance. Higher feeding volume may modify these relationships and have a protective role.