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Background Adequate enteral nutrition may be difficult to achieve early in neonates after cardiac surgery, but it is essential for growth, wound healing, and immune function.Objective To assess caloric intake in neonates receiving enteral nutrition after surgery.Methods A retrospective chart review was conducted of daily enteral caloric intake in the cardiac intensive care unit of a tertiary children's hospital. Data on the institution of enteral feeding and the discontinuation of parenteral nutrition were assessed for full-term neonates who had undergone cardiac surgery.Results Caloric intake was assessed in 100 patients, 52 with biventricular cardiac defects and 48 with a functional single ventricle. The median duration of stay in the cardiac intensive care unit was 13 days (range, 4-69), and patients received enteral feeding exclusively for a median of 5 days (range, 1-43). In total, 705 patient days were evaluated. The median caloric intake per day was 93 kcal/kg (range, 43-142). A goal of 100 kcal/kg was achieved for 48.4% of patient days and 120 kcal/kg for only 19.7% of patient days. Median weight change for the period of enteral feeding was -20 g (range, -775 to 1485 g).Conclusions Enteral feeding alone is often suboptimal after neonatal cardiac surgery. New strategies to improve caloric intake may enhance postoperative recovery. [ABSTRACT FROM AUTHOR]

The objectives of this study were to determine the validity of the grade of mitral regurgitation (MR) as imaged by intraoperative transesophageal echocardiography (TEE) in predicting the grade of MR at follow-up. Intraoperative TEE and corresponding follow-up transthoracic studies were retrospectively reviewed and the regurgitant jet area to left atrial area ratio was used to quantify the MR. Patient records were reviewed to identify factors contributing to the development of a certain grade of MR. Intraoperative TEE was useful in detecting severe MR that required further repair at the same time. However, discrepancy in the grade of MR at follow-up was noted in 47% of patients (21 of 47) and unchanged grade of MR was found only in 53% of patients (26 of 47). Blood pressures were significantly lower and heart rates higher intraoperatively. Initial preoperative grade of MR and type of atrioventricular canal defect did not predispose for a particular grade of MR at follow-up. The grade of MR by intraoperative TEE does not predict the grade of MR at follow-up as imaged by transthoracic echocardiography. [ABSTRACT FROM AUTHOR]

Severe fetal hypoxia poses a significant risk to lung development resulting in severe postnatal complications. Existing chronic hypoxia animal models lack the ability to achieve pathologically reduced fetal oxygen without compromising animal development, placental blood flow, or maternal health. Using an established model of isolated chronic hypoxia involving the Extrauterine Environment for Neonatal Development (EXTEND), we are able to investigate the direct impact of fetal hypoxia on lung development. Oxygen delivery to preterm fetal lambs (105-110 days GA) delivered by cesarean section was reduced, and animals were supported on EXTEND through the canalicular or saccular stage of lung development. Fetal lambs in hypoxic conditions showed significant growth restriction compared to their normoxic counterparts. We also observed modest aberrant vascular remodeling in the saccular group after hypoxic conditions with decreased macrovessel numbers, microvascular endothelial cell numbers, and increased peripheral vessel muscularization. In addition, fetal hypoxia resulted in enlarged distal airspaces and decreased septal wall volume. Moreover, there was a reduction in mature SFTPB and processed SFTPC protein expression concomitant with a decrease in AT2 cell number. These findings demonstrate that maternally-independent fetal hypoxia predominantly impacts distal airway development, AT2 cell number, and surfactant production with mild effects on the vasculature.

Fetal brain size is decreased in some children with complex CHDs, and the distribution of blood and accompanying oxygen and nutrients is regionally skewed from early fetal life dependent on the CHD. In transposition of the great arteries, deoxygenated blood preferentially runs to the brain, whereas the more oxygenated blood is directed towards the lungs and the abdomen. Knowledge of whether this impacts intrauterine organ development is limited. We investigated lung, liver, and total intracranial volume in fetuses with transposition of the great arteries using MRI.Eight fetuses with dextro-transposition and without concomitant disease or chromosomal abnormalities and 42 fetuses without CHD or other known diseases were scanned once or twice at gestational age 30 through 39 weeks. The MRI scans were conducted on a 1.5T system, using a 2D balanced steady-state free precession sequence. Slices acquired covered the entire fetus, slice thickness was 10 mm, pixel size 1.5 × 1.5 mm, and scan duration was 30 sec.The mean lung z score was significantly larger in fetuses with transposition compared with those without a CHD; mean difference is 1.24, 95% CI:(0.59;1.89), p < 0.001. The lung size, corrected for estimated fetal weight, was larger than in the fetuses without transposition; mean difference is 8.1 cm 3 /kg, 95% CI:(2.5;13.7 cm 3 /kg), p = 0.004.In summary, fetuses with dextro-transposition of the great arteries had both absolute and relatively larger lung volumes than those without CHD. No differences were seen in liver and total intracranial volume. Despite the small number of cases, the results are interesting and warrant further investigation.

Objective: It is unclear how extracorporeal membrane oxygenation use varies across paediatric cardiac surgical programmes and how it relates to post-operative mortality. We aimed to determine hospital-level variation in post-operative extracorporeal membrane oxygenation use and its association with case-mix adjusted mortality., Methods: Retrospective analysis of 37 hospitals contributing to the Pediatric Cardiac Critical Care Consortium clinical registry from 1 August 2014 to 31 December 2019. Hospitalisations including cardiothoracic surgery and post-operative admission to paediatric cardiac ICUs were included. Two-level multivariable logistic regression with hospital random effect was used to determine case-mix adjusted post-operative extracorporeal membrane oxygenation use rates and in-hospital mortality. Hospitals were grouped into extracorporeal membrane oxygenation use tertiles, and mortality was compared across tertiles., Results: There were 43,640 eligible surgical hospitalisations; 1397 (3.2%) included at least one post-operative extracorporeal membrane oxygenation run. Case-mix adjusted extracorporeal membrane oxygenation rates varied more than sevenfold (0.9-6.9%) across hospitals, and adjusted mortality varied 10-fold (0-5.5%). Extracorporeal membrane oxygenation rates were 2.0%, 3.5%, and 5.2%, respectively, for low, middle, and high extracorporeal membrane oxygenation use tertiles ( P < 0.0001), and mortality rates were 1.9%, 3.0%, and 3.1% ( p < 0.0001), respectively. High extracorporeal membrane oxygenation use hospitals were more likely to initiate extracorporeal membrane oxygenation support intraoperatively (1.6% vs. 0.6% low and 1.1% middle, p < 0.0001). Extracorporeal membrane oxygenation indications were similar across hospital tertiles. When extracorporeal cardiopulmonary resuscitation was excluded, variation in extracorporeal membrane oxygenation use rates persisted (1.5%, 2.6%, 3.8%, p < 0.001)., Conclusions: There is hospital variation in adjusted post-operative extracorporeal membrane oxygenation use after paediatric cardiac surgery and a significant association with adjusted post-operative mortality. These findings suggest that post-operative extracorporeal membrane oxygenation use could be a complementary quality metric to mortality to assess performance of cardiac surgical programmes.

Previous research suggests that individuals with 22q11.2 deletion syndrome (DS) have an increased risk of bleeding following cardiac surgery. However, current guidelines for management of patients with 22q11.2DS do not provide specific recommendations for perioperative management. This study sought to identify specific risk factors for bleeding in this patient population. Examine the factors determining bleeding and transfusion requirements in patients with 22q11.2DS undergoing cardiac surgery. This was a single center review of patients who underwent cardiac surgery at the Children's Hospital of Philadelphia from 2000 to 2016. Data was extracted from the medical record. Frequency of bleeding events, laboratory values, and transfusion requirements were compared. We included 226 patients with 22q11.2DS and 506 controls. Bleeding events were identified in 13 patients with 22q11.2DS (5.8%) and 27 controls (5.3%). Platelet counts were lower among patients with 22q11.2DS than in control patients, but not statistically different comparing bleeding to not bleeding. Patients with 22q11.2DS received more transfusions (regardless of bleeding status). However, multivariate analysis showed only procedure type was associated with increased risk of bleeding ( p  = .012). The overall risk of bleeding when undergoing cardiac surgery is not different in patients with 22q11.2DS compared to non-deleted patients. Though platelet counts were lower in patients with 22q11.2DS, only procedure type was significantly associated with an increased risk of bleeding.

Importance: Persistent hypothermia after cardiopulmonary bypass (CPB) in neonates with congenital heart defects (CHD) has been historically considered benign despite lack of evidence on its prognostic significance., Objectives: Examine associations between the magnitude and pattern of unintentional postoperative hypothermia and odds of complications in neonates with CHD undergoing CPB., Design: Retrospective cohort study., Setting: Single northeastern U.S., urban pediatric quaternary care center with an established cardiac surgery program., Participants: Population-based sample of neonates greater than or equal to 34 weeks gestation undergoing their first CPB between 2015 and 2019., Interventions: None., Main Outcomes and Measurements: Hourly temperature measurements for the first 48 postoperative hours were extracted from inpatient medical records, and clinical characteristics and outcomes were accessed through the local patient registry. Group-based trajectory modeling (GBTM) identified latent temporal temperature trajectories. Associations of trajectories with outcomes were assessed using multivariable binary logistic regression. Outcomes (postoperative complications) were manually adjudicated by experts or were predefined by the patient registry., Results: Four hundred fifty neonates met inclusion criteria. Their mean (sd) gestational age was 38 weeks (1.3), mean (sd) birth weight was 3.19 kilograms (0.55), median (interquartile range) surgical age was 4.7 days (3.3-7.0), 284 of 450 (63%) were male, and 272 of 450 (60%) were White. GBTM identified three distinct curvilinear temperature trajectories: persistent hypothermia (n = 38, 9%), resolving hypothermia (n = 233, 52%), and normothermia (n = 179, 40%). Compared with the normothermic group, those with persistent hypothermia had significantly higher odds of cardiac arrest, actionable arrhythmia, delayed first successful extubation, prolonged cardiac ICU length of stay, very poor weight gain, and 30-day hospital mortality. The persistent hypothermia group was characterized by greater odds of having a lower gestational age, more prevalent neurologic abnormalities, more unplanned reoperations, and a low surgical mortality risk assessment., Conclusions: Persistent postoperative hypothermia in neonates after CPB is independently associated with having greater odds of complications. Recovery patterns from postoperative hypothermia may be a clinically useful marker to identify patient instability in neonates. Additional research is needed for causal modeling and prospective validation before clinical adoption., Competing Interests: Dr. Henker is a member of the Critical Care Explorations editorial board. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: We previously demonstrated cerebral mitochondrial dysfunction in neonatal swine immediately following a period of full-flow cardiopulmonary bypass (CPB). The extent to which this dysfunction persists in the postoperative period and its correlation with other markers of cerebral bioenergetic failure and injury is unknown. We utilized a neonatal swine model to investigate the early evolution of mitochondrial function and cerebral bioenergetic failure after CPB. Methods: Twenty piglets (mean weight 4.4 ± 0.5 kg) underwent 3 h of CPB at 34 °C via cervical cannulation and were followed for 8, 12, 18, or 24 h (n = 5 per group). Markers of brain tissue damage (glycerol) and bioenergetic dysfunction (lactate to pyruvate ratio) were continuously measured in cerebral microdialysate samples. Control animals (n = 3, mean weight 4.1 ± 1.2 kg) did not undergo cannulation or CPB. Brain tissue was extracted immediately after euthanasia to obtain ex-vivo cortical mitochondrial respiration and frequency of cortical microglial nodules (indicative of cerebral microinfarctions) via neuropathology. Results: Both the lactate to pyruvate ratio ( P  < .0001) and glycerol levels ( P  = .01) increased in cerebral microdialysate within 8 h after CPB. At 24 h post-CPB, cortical mitochondrial respiration was significantly decreased compared with controls ( P  = .046). The presence of microglial nodules increased throughout the study period (24 h) ( P  = .01, R 2  = 0.9). Conclusion: CPB results in impaired cerebral bioenergetics that persist for at least 24 h. During this period of bioenergetic impairment, there may be increased susceptibility to secondary injury related to alterations in metabolic delivery or demand, such as hypoglycemia, seizures, and decreased cerebral blood flow., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Children with congenital heart disease (CHD) demonstrate long-term neurodevelopmental impairments. We investigated contrast-enhanced ultrasound (CEUS) cerebral perfusion in a fetal animal model exposed to sub-physiologic oxygen at equivalent levels observed in human fetuses with CHD., Methods: Fifteen fetal lambs [hypoxic animals (n = 9) and normoxic controls (n = 6)] maintained in an extrauterine environment underwent periodic brain CEUS. Perfusion parameters including microvascular flow velocity (MFV), transit time, and microvascular blood flow (MBF) were extrapolated from a standardized plane; regions of interest (ROI) included whole brain, central/thalami, and peripheral parenchymal analyses. Daily echocardiographic parameters and middle cerebral artery (MCA) pulsatility indices (PIs) were obtained., Results: Hypoxic lambs demonstrated decreased MFV, increased transit time, and decreased MBF (p = 0.026, p = 0.016, and p < 0.001, respectively) by whole brain analyses. MFV and transit time were relatively preserved in the central/thalami (p = 0.11, p = 0.08, p = 0.012, respectively) with differences in the peripheral parenchyma (all p < 0.001). In general, cardiac variables did not correlate with cerebral CEUS perfusion parameters. Hypoxic animals demonstrated decreased MCA PI compared to controls (0.65 vs. 0.78, respectively; p = 0.027)., Conclusion: Aberrations in CEUS perfusion parameters suggest that in environments of prolonged hypoxia, there are regional microvascular differences incompletely characterized by MCA interrogation offering insights into fetal conditions which may contribute to patient outcomes., Impact: This work utilizes CEUS to study cerebral microvascular perfusion in a unique fetal animal model subjected to chronic hypoxic conditions equal to fetuses with congenital heart disease. CEUS demonstrates altered parameters with regional differences that are incompletely characterized by MCA Doppler values. These findings show that routine MCA Doppler interrogation may be inadequate in assessing microvascular perfusion differences. To our knowledge, this study is the first to utilize CEUS to assess microvascular perfusion in this model. The results offer insight into underlying conditions and physiological changes which may contribute to known neurodevelopmental impairments in those with congenital heart disease., (© 2024. The Author(s).)

Objective: The thoracic duct is the largest lymphatic vessel in the body, and carries fluid and nutrients absorbed in abdominal organs to the central venous circulation. Thoracic duct obstruction can cause significant failure of the lymphatic circulation (i.e., protein-losing enteropathy, plastic bronchitis, etc.). Surgical anastomosis between the thoracic duct and central venous circulation has been used to treat thoracic duct obstruction but cannot provide lymphatic decompression in patients with superior vena cava obstruction or chronically elevated central venous pressures (e.g., right heart failure, single ventricle physiology, etc.). Therefore, this preclinical feasibility study sought to develop a novel and optimal surgical technique for creating a thoracic duct-to-pulmonary vein lymphovenous anastomosis (LVA) in swine that could remain patent and preserve unidirectional lymphatic fluid flow into the systemic venous circulation to provide therapeutic decompression of the lymphatic circulation even at high central venous pressures., Methods: A thoracic duct-to-pulmonary vein LVA was attempted in 10 piglets (median age 80 [IQR 80-83] days; weight 22.5 [IQR 21.4-26.8] kg). After a right thoracotomy, the thoracic duct was mobilized, transected, and anastomosed to the right inferior pulmonary vein. Animals were systemically anticoagulated on post-operative day 1. Lymphangiography was used to evaluate LVA patency up to post-operative day 7., Results: A thoracic duct-to-pulmonary vein LVA was successfully completed in 8/10 (80.0%) piglets, of which 6/8 (75.0%) survived to the intended study endpoint without any complication (median 6 [IQR 4-7] days). Initially, 2/10 (20.0%) LVAs were aborted intraoperatively, and 2/10 (20.0%) animals were euthanized early due to post-operative complications. However, using an optimized surgical technique, the success rate for creating a thoracic duct-to-pulmonary vein LVA in six animals was 100%, all of which survived to their intended study endpoint without any complications (median 6 [IQR 4-7] days). LVAs remained patent for up to seven days., Conclusion: A thoracic duct-to-pulmonary vein LVA can be completed safely and remain patent for at least one week with systemic anticoagulation, which provides an important proof-of-concept that this novel intervention could effectively offload the lymphatic circulation in patients with lymphatic failure and elevated central venous pressures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lymphatic failure is a broad term that describes the lymphatic circulation's inability to adequately transport fluid and solutes out of the interstitium and into the systemic venous circulation, which can result in dysfunction and dysregulation of immune responses, dietary fat absorption, and fluid balance maintenance. Several investigations have recently elucidated the nexus between lymphatic failure and congenital heart disease, and the associated morbidity and mortality is now well-recognized. However, the precise pathophysiology and pathogenesis of lymphatic failure remains poorly understood and relatively understudied, and there are no targeted therapeutics or interventions to reliably prevent its development and progression. Thus, there is growing enthusiasm towards the development and application of novel percutaneous and surgical lymphatic interventions. Moreover, there is consensus that further investigations are needed to delineate the underlying mechanisms of lymphatic failure, which could help identify novel therapeutic targets and develop innovative procedures to improve the overall quality of life and survival of these patients. With these considerations, this review aims to provide an overview of the lymphatic circulation and its vasculature as it relates to current understandings into the pathophysiology and pathogenesis of lymphatic failure in patients with congenital heart disease, while also summarizing strategies for evaluating and managing lymphatic complications, as well as specific areas of interest for future translational and clinical research efforts., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: In 2004, we reported improved early survival for patients with functional single ventricle anatomy and total anomalous pulmonary venous connection. This study sought to discover if outcomes have been ameliorated in the contemporary era., Methods: This was a single-center review of patients with single ventricle anatomy and total anomalous pulmonary venous connection who were admitted from 1984 to 2021. The cohort was divided into similarly sized groups by date of admission: Era 1: 1984 to 1992, Era 2: 1993 to 2007, and Era 3: 2008 to 2021. Survival was compared, and Cox proportional hazards models were used to evaluate the likelihood of mortality., Results: We included 190 patients with single ventricle anatomy and total anomalous pulmonary venous connection. Unbalanced atrioventricular canal defect (70%) was the most common primary diagnosis. The most common type of total anomalous pulmonary venous connection was supracardiac (49%). Approximately one-third (32%) of patients had pulmonary venous obstruction. There were no significant differences in patient characteristics across eras. Early survival after initial palliative operation improved between Eras 1 and 2, and then remained stable in Era 3. Overall survival improved from Era 1 to Eras 2 and 3 (P < .001), but not between Era 2 and 3. Survival to 10 years by Eras 1 to 3 was 15%, 51%, and 54%, respectively. The anatomic features associated with worse survival were hypoplastic left heart syndrome diagnosis (hazard ratio, 1.60; 1.04-2.57) and pulmonary venous obstruction (hazard ratio, 1.80; 1.24-2.69)., Conclusions: Overall survival for patients with single ventricle anatomy and total anomalous pulmonary venous connection has plateaued since the early 2000s. Even in the most recent era, survival to age 10 years remains less than 60%. Risk factors for mortality include the diagnosis of hypoplastic left heart syndrome and pulmonary venous obstruction. Further studies should focus on identification of the pathophysiological factors underlying the increased mortality., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Optimal oxygen management during pediatric cardiopulmonary bypass (CPB) is unknown. We previously demonstrated an increase in cortical mitochondrial reactive oxygen species and decreased mitochondrial function after CPB using hyperoxic oxygen management. This study investigates whether controlled oxygenation (normoxia) during CPB reduces cortical mitochondrial dysfunction and oxidative injury. Ten neonatal swine underwent three hours of continuous CPB at 34 °C (flow > 100 mL/kg/min) via cervical cannulation targeting a partial pressure of arterial oxygen (PaO 2 ) goal < 150 mmHg (normoxia, n = 5) or >300 mmHg (hyperoxia, n = 5). The animals underwent continuous hemodynamic monitoring and serial arterial blood sampling. Cortical microdialysate was serially sampled to quantify the glycerol concentration (represents neuronal injury) and lactate-to-pyruvate ratio (represents bioenergetic dysfunction). The cortical tissue was analyzed via high-resolution respirometry to quantify mitochondrial oxygen consumption and reactive oxygen species generation, and cortical oxidized protein carbonyl concentrations were quantified to assess for oxidative damage. Serum PaO 2 was higher in hyperoxia animals throughout CPB ( p < 0.001). There were no differences in cortical glycerol concentration between groups ( p > 0.2). The cortical lactate-to-pyruvate ratio was modestly elevated in hyperoxia animals ( p < 0.03) but the values were not clinically significant (<30). There were no differences in cortical mitochondrial respiration ( p = 0.48), protein carbonyls ( p = 0.74), or reactive oxygen species generation ( p = 0.93) between groups. Controlled oxygenation during CPB does not significantly affect cortical mitochondrial function or oxidative injury in the acute setting. Further evaluation of the short and long-term effects of oxygen level titration during pediatric CPB on cortical tissue and other at-risk brain regions are needed, especially in the presence of cyanosis.

Objective: To determine whether early structural brain trajectories predict early childhood neurodevelopmental deficits in complex CHD patients and to assess relative cumulative risk profiles of clinical, genetic, and demographic risk factors across early development. Study Design : Term neonates with complex CHDs were recruited at Texas Children's Hospital from 2005-2011. Ninety-five participants underwent three structural MRI scans and three neurodevelopmental assessments. Brain region volumes and white matter tract fractional anisotropy and radial diffusivity were used to calculate trajectories: perioperative, postsurgical, and overall. Gross cognitive, language, and visuo-motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development and with the Wechsler Preschool and Primary Scale of Intelligence and Beery-Buktenica Developmental Test of Visual-Motor Integration. Multi-variable models incorporated risk factors. Results: Reduced overall period volumetric trajectories predicted poor language outcomes: brainstem ((β, 95% CI) 0.0977, 0.0382-0.1571; p = 0.0022) and white matter (0.0023, 0.0001-0.0046; p = 0.0397) at 5 years; brainstem (0.0711, 0.0157-0.1265; p = 0.0134) and deep grey matter (0.0085, 0.0011-0.0160; p = 0.0258) at 3 years. Maternal IQ was the strongest contributor to language variance, increasing from 37% at 1 year, 62% at 3 years, and 81% at 5 years. Genetic abnormality's contribution to variance decreased from 41% at 1 year to 25% at 3 years and was insignificant at 5 years. Conclusion: Reduced postnatal subcortical-cerebral white matter trajectories predicted poor early childhood neurodevelopmental outcomes, despite high contribution of maternal IQ. Maternal IQ was cumulative over time, exceeding the influence of known cardiac and genetic factors in complex CHD, underscoring the importance of heritable and parent-based environmental factors.

Background: Cholestasis characterised by conjugated hyperbilirubinemia is a marker of hepatobiliary dysfunction following neonatal cardiac surgery. We aimed to characterise the incidence of conjugated hyperbilirubinemia following neonatal heart surgery and examine the effect of conjugated hyperbilirubinemia on post-operative morbidity and mortality., Methods: This was a retrospective study of all neonates who underwent surgery for congenital heart disease (CHD) at our institution between 1/1/2010 and 12/31/2020. Patient- and surgery-specific data were abstracted from local registry data and review of the medical record. Conjugated hyperbilirubinemia was defined as perioperative maximum conjugated bilirubin level > 1 mg/dL. The primary outcome was in-hospital mortality. Survival analysis was conducted using the Kaplan-Meier survival function., Results: Conjugated hyperbilirubinemia occurred in 8.5% of patients during the study period. Neonates with conjugated hyperbilirubinemia were more likely to be of younger gestational age, lower birth weight, and non-Caucasian race (all p < 0.001). Patients with conjugated hyperbilirubinemia were more likely to have chromosomal and non-cardiac anomalies and require ECMO pre-operatively. In-hospital mortality among patients with conjugated hyperbilirubinemia was increased compared to those without (odds ratio 5.4). Post-operative complications including mechanical circulatory support, reoperation, prolonged ventilator dependence, and multi-system organ failure were more common with conjugated hyperbilirubinemia (all p < 0.04). Patients with higher levels of conjugated bilirubin had worst intermediate-term survival, with patients in the highest conjugated bilirubin group (>10 mg/dL) having a 1-year survival of only 6%., Conclusions: Conjugated hyperbilirubinemia is associated with post-operative complications and worse survival following neonatal heart surgery. Cholestasis is more common in patients with chromosomal abnormalities and non-cardiac anomalies, but the underlying mechanisms have not been delineated.

The Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database (CHSD) continues to be the most comprehensive database of congenital and pediatric cardiothoracic surgical procedures in the world and contains information on 664,210 operations as of June 30, 2023. The 35th harvest of the STS CHSD data was undertaken in Spring 2023, spanning the 4-year period January 1, 2019, through December 31, 2022, and included 144,919 operations performed at 114 participating sites in North America. The harvest analysis was successfully executed by the STS Research and Analytic Center. The overall unadjusted mortality rate was 2.68% and has remained stable over the 4 years included in the current harvest window. Mortality is highest in neonates (7.4%) and lowest in children (1.1%). As in prior analyses, observed mortality and postoperative length of stay in the database increase with an increase in STS-European Association for Cardio-Thoracic Surgery (STAT) Congenital Heart Surgery Mortality Categories. This quality report summarizes contemporary outcomes, provides the odds ratios for the CHSD risk model variables based on this analysis, and describes on-going efforts to improve data collection and augment analytical approaches. Lastly, 5 research publications completed in the last year using data from the CHSD are also summarized., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Importance: Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years., Objectives: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD., Design, Setting, and Participants: This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024., Intervention: Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age., Main Outcomes and Measures: The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment., Results: The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70)., Conclusions and Relevance: In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex., Trial Registration: ClinicalTrials.gov Identifier: NCT02133573.

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., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Studies show that an impaired maternal-fetal environment (iMFE) increases the mortality risk in children with single-ventricle congenital heart defects (CHDs). We investigated the impact of an iMFE on death in children with various surgically corrected CHDs., Methods and Results: In this nationwide register-based study, we examined the association between an iMFE (including preeclampsia, gestational hypertension, gestational diabetes, maternal smoking during pregnancy) and death in a large cohort of children with surgically corrected CHDs in Denmark (1994-2018). Survival analysis was done using Cox regression, adjusted for confounding and mediating covariates. The cohort included 3304 children: 1662 (50.3%) with minor CHD and 1642 (49.7%) with major CHD. Among them, 792 (24%) children were exposed to an iMFE. During the study, there were 290 deaths: 71 (9.3%) in children exposed to an iMFE and 219 (8.7%) in those unexposed. There were no differences in mortality risk between children with CHD exposed to an iMFE and those unexposed (hazard ratio [HR], 1.12 [95% CI, 0.86-1.47]; P =0.4). This was consistent across subgroups, including minor CHD (HR, 0.76 [95% CI, 0.39-1.47]; P =0.4), major CHD (HR, 1.23 [95% CI, 0.92-1.64]; P =0.2), and hypoplastic left heart syndrome/univentricular heart (HR, 1.08 [95% CI, 0.64-1.85]; P =0.8)., Conclusions: Impairment of the maternal-fetal environment did not impact the mortality rate in children with CHD undergoing operation in Denmark from 1994 to 2018. We believe the cause of these discrepant findings to previous studies may be due to differences in the composition of CHD and prenatal maternal health care and health status of the population.

Objectives: The primary objectives were to examine utilization of the Hybrid versus the Norwood procedure for patients with hypoplastic left heart syndrome or variants and the impact on hospital mortality. The Hybrid procedure was 1st used at our institution in 2004., Methods: Review of all subjects undergoing the Norwood or Hybrid procedure between 1 January 1984 and 31 December 2022. The study period was divided into 8 eras: era 1, 1984-1988; era 2, 1989-1993; era 3, 1994-1998; era 4, 1999-2003; era 5, 2004-2008; era 6, 2009-2014; era 7, 2015-2018 and era 8, 2019-2022. The primary outcome was in-hospital mortality. Mortality rates were computed using standard binomial proportions with 95% confidence intervals. Rates across eras were compared using an ordered logistic regression model with and adjusted using the Tukey-Kramer post-hoc procedure for multiple comparisons. In the risk-modelling phase, logistic regression models were specified and tested., Results: The Norwood procedure was performed in 1899 subjects, and the Hybrid procedure in 82 subjects. Use of the Hybrid procedure increased in each subsequent era, reaching 30% of subjects in era 8. After adjustment for multiple risk factors, use of the Hybrid procedure was significantly and positively associated with hospital mortality., Conclusions: Despite the increasing use of the Hybrid procedure, overall mortality for the entire cohort has plateaued. After adjustment for risk factors, use of the Hybrid procedure was significantly and positively associated with mortality compared to the Norwood procedure., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: Volatile organic compounds (VOCs) are used in the sterilization and manufacture of medical equipment. These compounds have high vapor pressures with low water solubility and are emitted as gases from solids or liquids. They can be mutagenic, neurotoxic, genotoxic, and/or carcinogenic. Safe limits of exposure are not known for neonates. This study examined determinants of exposure in newborns undergoing cardiac surgery., Methods: Twenty metabolites of 16 VOCs (eg, xylene, cyanide, acrolein, acrylonitrile, N, N-dimethylformamide, 1,3-butadiene, styrene, and benzene) were measured as metabolites in daily urine samples collected from 10 neonates undergoing cardiac operations (n = 150 samples). Metabolites were quantified using reversed-phase ultra-high performance liquid chromatography and electrospray ionization tandem mass spectrometry. Repeated measures analysis of covariance was performed for each metabolite to examine associations with use of medical devices., Results: At least 3 metabolites were detected in every sample. The median number of metabolites detected in each sample was 14 (range, 3-15). In a model controlling for other factors, the use of extracorporeal membrane oxygenation was associated with significantly (P ≤ .05) greater metabolite levels of acrolein, acrylonitrile, ethylene oxide, propylene oxide, styrene, and ethylbenzene. Patients breathing ambient air had greater levels of metabolites of acrolein, xylene, N,N-dimethylformamide, methyl isocyanate, cyanide, 1,3-butadiene (all P ≤ .05)., Conclusions: Exposure to volatile organic compounds is pervasive in newborns undergoing cardiac surgery. Sources of exposure likely include medical devices and inhalation from the air in the intensive care unit. The contribution of VOC exposure during cardiac surgery in newborns to adverse outcomes warrants further evaluation., (Copyright © 2024. Published by Elsevier Inc.)

Background: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis., Objective: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome., Study Design: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 deletion syndrome by 1 year of age with or without congenital heart disease; those with prenatal diagnosis or suspicion (suggestive ultrasound findings and/or high-risk cell-free fetal DNA screen for 22q11.2 deletion syndrome with postnatal confirmation) were compared with those with postnatal diagnosis. Perinatal management, cardiac and noncardiac morbidity, and mortality by 1 year were assessed. Outcomes were adjusted for presence of critical congenital heart disease, gestational age at birth, and site., Results: A total of 625 fetuses, neonates, or infants with 22q11.2 deletion syndrome (53.4% male) were included: 259 fetuses were prenatally diagnosed (156 [60.2%] were live-born) and 122 neonates were prenatally suspected with postnatal confirmation, whereas 244 infants were postnatally diagnosed. In the live-born cohort (n=522), 1-year mortality was 5.9%, which did not differ between groups but differed by the presence of critical congenital heart disease (hazard ratio, 4.18; 95% confidence interval, 1.56-11.18; P<.001) and gestational age at birth (hazard ratio, 0.78 per week; 95% confidence interval, 0.69-0.89; P<.001). Adjusting for critical congenital heart disease and gestational age at birth, the prenatal cohort was less likely to deliver at a local community hospital (5.1% vs 38.2%; odds ratio, 0.11; 95% confidence interval, 0.06-0.23; P<.001), experience neonatal cardiac decompensation (1.3% vs 5.0%; odds ratio, 0.11; 95% confidence interval, 0.03-0.49; P=.004), or have failure to thrive by 1 year (43.4% vs 50.3%; odds ratio, 0.58; 95% confidence interval, 0.36-0.91; P=.019)., Conclusion: Prenatal detection of 22q11.2 deletion syndrome was associated with improved delivery management and less cardiac and noncardiac morbidity, but not mortality, compared with postnatal detection., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess the diagnostic yield of exome sequencing (ES) in pediatric cardiomyopathy., Study Design: A single-institution, retrospective chart review of 91 patients with pediatric cardiomyopathy was performed. While pediatric cardiomyopathy is often genetic in nature, no genetic test is recommended as standard of care. All our patients were diagnosed with cardiomyopathy and evaluated by a medical geneticist between January 2010 through September 2022. Demographic information and clinical data were abstracted., Results: Of 91 patients with pediatric cardiomyopathy, 36 (39.6%) received a diagnosis by ES. Twenty-two (61.1%) of these diagnoses would have been missed on cardiac multigene panel testing. The diagnostic yield for cardiomyopathy presenting under 1 year of age was 38.3%, while the yield for patients over 1 year of age was 41.9%., Conclusions: ES has a high diagnostic yield in pediatric cardiomyopathy compared with a gene panel. Over 60% of patients with diagnosis by ES would not have received their molecular genetic diagnosis if only multigene panel testing was sent. Diagnostic yield did not vary significantly between the subtypes of cardiomyopathy and patient age groups, highlighting the likely clinical utility of ES for all pediatric cardiomyopathy patients., Competing Interests: Declaration of Competing Interest Conflicts of Interest: The authors have no conflicts of interest to declare for this manuscript. Julia Keisling wrote the first draft of the manuscript. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript. The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)