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Background Methods Results Conclusion Trial Registration Patients with hypoplastic left heart syndrome undergo the comprehensive stage 2 procedure as the second stage in the hybrid approach toward Fontan circulation. The complexity of comprehensive stage 2 procedure is considered a potential limitation, and limited information is available on its anesthetic management. This study aims to address this gap.A single‐center retrospective cohort study analyzed 148 HLHS patients who underwent comprehensive stage 2 procedure, divided into Group A (stable condition, n = 116) and Group B (requiring preoperative intravenous inotropic therapy, n = 32). Demographic data, intraoperative hemodynamics, anesthetic management, and postoperative outcomes were collected.Etomidate (40%) was the most common induction agent, followed by esketamine (24%), midazolam (16%), and propofol (13%). Inhaled induction was rarely necessary (2%), occurring only in Group A patients. No statistical differences were found between groups for induction drug choice. Post‐cardiopulmonary bypass management included moderate hypoventilation, inhaled nitric oxide (100%), and hemodynamic support with milrinone (97%) and norepinephrine (77%). Group B patients more frequently required additional levosimendan (20%) and epinephrine (18%). Extracorporeal membrane oxygenation was necessary in 8 patients (5%) with no between‐group differences. Switching from fentanyl to remifentanil reduced postoperative ventilation time overall. However, Group B experienced significantly longer ventilation (6.3 vs. 3.5 h) and ICU stay (22 vs. 14 days). In‐hospital mortality was 5% overall (Group A: 4%, Group B: 9%). Long‐term survival analysis revealed a significant advantage for Group A.The use of short‐acting opioids and adjusted ventilation modes enables optimal pulmonary blood flow and rapid transition to spontaneous breathing. Differentiated hemodynamic support with milrinone, norepinephrine, supplemented by levosimendan and epinephrine in high‐risk patients, can mitigate the effects on the preoperatively volume‐loaded right ventricle. However, differences in long‐term survival probability were observed between groups.Local ethics committee, Medical Faculty, Justus‐Liebig‐University‐Giessen (Trial Code Number: 216/14). [ABSTRACT FROM AUTHOR]

This document presents a consensus opinion from the Fetal Heart Society on the use of acute maternal hyperoxygenation (MH) testing in fetal cardiology. The guidelines provided in the document aim to standardize the use of this testing in clinical practice and promote collaborative learning and research in the field. The document includes information on the timing of the test, fetal echocardiographic parameters to be assessed, indications for testing, and interpretation of findings. It also identifies areas for future research and includes a list of collaborating institutions. [Extracted from the article]

Background: The atrium augments ventricular function, but the significance of atrial function in hypoplastic left heart syndrome (HLHS) has not been well evaluated. Objective: We investigated the association of atrial reservoir strain (common atrial strain [CAS]) to death or need for transplantation in patients with HLHS. Methods: In this retrospective single‐center study, echocardiograms from three timepoints (pre‐stage 1 palliation [S1P], 4–8 weeks post‐S1P, and pre‐Glenn) were analyzed in infants with classic HLHS. Patients were separated based on transplant‐free survival to Fontan (survivors) versus death or heart transplant prior to Fontan (composite outcome). Echocardiographic parameters evaluated included CAS, right ventricle (RV) global longitudinal strain (RVGLS), RV fractional area change (FAC), and tricuspid annular plane systolic excursion (TAPSE). An equal variance t‐test, regression, and receiver operating characteristic (ROC) analyses were performed. Results: A total of 45 HLHS patients (25 survivors, 20 patients meeting endpoint) were included in this study. There were no significant differences in any of the functional parameters during the pre‐stage 1 or post‐stage 1 timepoints. Pre‐Glenn CAS and RVGLS were significantly worse in those meeting composite endpoint compared to survivors. CAS was significantly correlated to RVGLS during the pre‐S1P and pre‐Glenn timepoints. A pre‐Glenn CAS < 19.5 had an area under the curve of.78 and a 75% sensitivity and 83% specificity for death or need for transplantation. Conclusion: Pre‐Glenn CAS is significantly lower in patients with mortality or need for the transplantation prior to Fontan completion and may carry prognostic significance in patients with HLHS. [ABSTRACT FROM AUTHOR]

Background: Critical aortic stenosis (AS) in fetuses may progress to hypoplastic left heart syndrome (HLHS) with need for postnatal single ventricular (SV) palliation. Fetal aortic valvuloplasty (FAV) is performed to achieve postnatal biventricular (BV) circulation. However, the impact of FAV on fetal myocardial function is difficult to measure. Prediction of postnatal circulatory status and, therefore, counseling is challenging. Methods: Retrospective study of fetuses with critical AS who underwent FAV. Global Longitudinal Peak Systolic Strain (GLPSS) of the left ventricle (LV) and right ventricle (RV) were retrospectively analyzed before and after intervention. Fisher's Exact Test and Mann–Whitney-U Test were used for univariant statistical analysis. Results: 23 fetuses with critical AS were included. After intervention fetuses demonstrated more negative LV-GLPSS mean values post- vs. pre-intervention (− 5.36% vs. − 1.57%; p < 0.05). RV-GLPSS was decreased in all fetuses, there was no peri-interventional change. 20 fetuses were born alive. Postnatally, 10 had BV and 10 SV circulation. Improved post-interventional LV-GLPSS strain values correlated with BV outcome (p < 0.05). Pre-interventional continuous LV-GLPSS values correlated with postnatal SV vs. BV outcome (p < 0.05). Conclusion: In some fetuses, LV myocardial function assessed by speckle tracking echocardiography (STE) improves after FAV. Improved post-interventional LV-GLPSS correlates with biventricular postnatal outcome. Furthermore, pre-interventional LV- and RV-GLPSS correlate with postnatal outcome. Further studies are needed to asses, if pre-interventional STE parameters might predict which fetuses will benefit from FAV with postnatal BV circulation. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) represents a spectrum of inborn heart defects influenced by genetic and environmental factors. This study advances the field by analyzing gene expression profiles in 21,034 cardiac fibroblasts, 73,296 cardiomyocytes, and 35,673 endothelial cells, utilizing single-cell level analysis and machine learning techniques. Six CHD conditions: dilated cardiomyopathy (DCM), donor hearts (used as healthy controls), hypertrophic cardiomyopathy (HCM), heart failure with hypoplastic left heart syndrome (HF_HLHS), Neonatal Hypoplastic Left Heart Syndrome (Neo_HLHS), and Tetralogy of Fallot (TOF), were investigated for each cardiac cell type. Each cell sample was represented by 29,266 gene features. These features were first analyzed by six feature-ranking algorithms, resulting in several feature lists. Then, these lists were fed into incremental feature selection, containing two classification algorithms, to extract essential gene features and classification rules and build efficient classifiers. The identified essential genes can be potential CHD markers in different cardiac cell types. For instance, the LASSO identified key genes specific to various heart cell types in CHD subtypes. FOXO3 was found to be up-regulated in cardiac fibroblasts for both Dilated and hypertrophic cardiomyopathy. In cardiomyocytes, distinct genes such as TMTC1, ART3, ARHGAP24, SHROOM3, and XIST were linked to dilated cardiomyopathy, Neo-Hypoplastic Left Heart Syndrome, hypertrophic cardiomyopathy, HF-Hypoplastic Left Heart Syndrome, and Tetralogy of Fallot, respectively. Endothelial cell analysis further revealed COL25A1, NFIB, and KLF7 as significant genes for dilated cardiomyopathy, hypertrophic cardiomyopathy, and Tetralogy of Fallot. LightGBM, Catboost, MCFS, RF, and XGBoost further delineated key genes for specific CHD subtypes, demonstrating the efficacy of machine learning in identifying CHD-specific genes. Additionally, this study developed quantitative rules for representing the gene expression patterns related to CHDs. This research underscores the potential of machine learning in unraveling the molecular complexities of CHD and establishes a foundation for future mechanism-based studies. [ABSTRACT FROM AUTHOR]

Patients with heterotaxy syndrome and congenital heart disease (CHD) experience inferior cardiac surgical outcomes. Heart transplantation outcomes are understudied, however, particularly compared to non-CHD patients. Data from UNOS and PHIS were used to identify 4803 children (< 18 years) undergoing first-time heart transplant between 2003 and 2022 with diagnoses of heterotaxy (n = 278), other-CHD (n = 2236), and non-CHD cardiomyopathy (n = 2289). Heterotaxy patients were older (median 5 yr) and heavier (median 17 kg) at transplant than other-CHD (median 2 yr and 12 kg), and younger and lighter than cardiomyopathy (median 7 yr and 24 kg) (all p < 0.001). UNOS status 1A/1 at listing was not different between groups (65–67%; p = 0.683). At transplant, heterotaxy and other-CHD patients had similar rates of renal dysfunction (12 and 17%), inotropes (10% and 11%), and ventilator-dependence (19 and 18%). Compared to cardiomyopathy, heterotaxy patients had comparable renal dysfunction (9%, p = 0.058) and inotropes (46%, p = 0.097) but more hepatic dysfunction (17%, p < 0.001) and ventilator-dependence (12%, p = 0.003). Rates of ventricular assist device (VAD) were: heterotaxy-10%, other-CHD-11% (p = 0.839 vs. heterotaxy), cardiomyopathy-37% (p < 0.001 vs. heterotaxy). The 1-year incidence of acute rejection post-transplant was comparable between heterotaxy and others (p > 0.05). While overall post-transplant survival was significantly worse for heterotaxy than others (p < 0.05 vs. both), conditional 1-year survival was comparable (p > 0.3 vs. both). Children with heterotaxy syndrome experience inferior post-heart transplant survival, although early mortality appears to influence this trend, with 1-year survivors having equivalent outcomes. Given similar pre-transplant clinical status to others, heterotaxy patients are potentially under risk-stratified. Increased VAD utilization and pre-transplant end-organ function optimization may portend improved outcomes. [ABSTRACT FROM AUTHOR]

Treatment of infants with hypoplastic left heart syndrome (HLHS) remains challenging, and those affected remain with significant risks for mortality and morbidity throughout their lifetimes. The maternal–fetal environment (MFE) has been shown to affect outcomes for infants with HLHS after the Norwood procedure. The hybrid procedure, comprised of both catheterization and surgical components, is a less invasive option for initial intervention compared to the Norwood procedure. It is unknown how the MFE impacts outcomes following the hybrid procedure. This is a single-center, retrospective study of infants born with HLHS who underwent hybrid palliation from January 2009 to August 2021. Predictor variables analyzed included fetal, maternal, and postnatal factors. The primary outcome was mortality prior to Stage II palliation. We studied a 144-subject cohort. There was a statistically significant difference in mortality prior to stage II palliation in infants with prematurity, small for gestational age, and aortic atresia subtype (p < 0.001, p = 0.009, and p = 0.008, respectively). There was no difference in mortality associated with maternal diabetes, hypertension, obesity, smoking or illicit drug use, or advanced maternal age. State and national area deprivation index scores were associated with increased risk of mortality in the entire cohort, such that infants born in areas with higher deprivation had a higher incidence of mortality. Several markers of an impaired MFE, including prematurity, small for gestational age, and higher deprivation index scores, are associated with mortality following hybrid palliation. Individual maternal comorbidities were not associated with higher mortality. The MFE may be a target for prenatal counseling and future interventions to improve pregnancy and neonatal outcomes in this population. [ABSTRACT FROM AUTHOR]

Objective We aimed to analyze somatic growth of patients after total cavopulmonary connection (TCPC) as well as to identify factors influencing postoperative catch-up growth. Methods A total of 309 patients undergoing TCPC at 4 years old or less between 1994 and 2021 were included. Weight for age z-score (WAZ) and height for age-z-score (HAZ) at TCPC and at postoperative time between 1 and 3 years were calculated. Factors influencing somatic growth were analyzed. Results Most frequent diagnosis and initial palliation were hypoplastic left heart syndrome (HLHS) (34%) and the Norwood procedure (51%), respectively. Median age and weight at TCPC were 2.0 (IQR: 1.7–2.5) years and 11.3 (10.5–12.7) kg, respectively. Median 519 days after TCPC, a significant increase in WAZ (−0.4 to −0.2, p < 0.001) was observed, but not in HAZ (−0.6 to −0.6, p = 0.38). Older age at TCPC (p < 0.001, odds ratio [OR]: 2.6) and HLHS (p = 0.007, OR: 2.2) were risks for low WAZ after TCPC. Older age at TCPC (p = 0.009, OR: 1.9) and previous Norwood procedure (p = 0.021, OR: 2.0) were risks for low HAZ after TCPC. Previous bidirectional cavopulmonary shunt (BCPS) was a protective factor for both WAZ (p = 0.012, OR: 0.06) and HAZ (p = 0.028, OR: 0.30) at TCPC. Conclusion In patients undergoing TCPC at the age of 4 years or less, a significant catch-up growth was observed in WAZ after TCPC, but not in HAZ. Previous BCPS resulted to be a protective factor for a better somatic development at TCPC. HLHSs undergoing Norwood were considered as risks for somatic development after TCPC. [ABSTRACT FROM AUTHOR]

Purposr: This study created 3D CFD models of the Norwood procedure for hypoplastic left heart syndrome (HLHS) using standard angiography and echocardiogram data to investigate the impact of shunt characteristics on pulmonary artery (PA) hemodynamics. Leveraging routine clinical data offers advantages such as availability and cost-effectiveness without subjecting patients to additional invasive procedures. Methods: Patient-specific geometries of the intrathoracic arteries of two Norwood patients were generated from biplane cineangiograms. "Virtual surgery" was then performed to simulate the hemodynamics of alternative PA shunt configurations, including shunt type (modified Blalock-Thomas-Taussig shunt (mBTTS) vs. right ventricle-to-pulmonary artery shunt (RVPAS)), shunt diameter, and pulmonary artery anastomosis angle. Left-right pulmonary flow differential, Qp/Qs, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) were evaluated. Results: There was strong agreement between clinically measured data and CFD model output throughout the patient-specific models. Geometries with a RVPAS tended toward more balanced left-right pulmonary flow, lower Qp/Qs, and greater TAWSS and OSI than models with a mBTTS. For both shunt types, larger shunts resulted in a higher Qp/Qs and higher TAWSS, with minimal effect on OSI. Low TAWSS areas correlated with regions of low flow and changing the PA-shunt anastomosis angle to face toward low TAWSS regions increased TAWSS. Conclusion: Excellent correlation between clinically measured and CFD model data shows that 3D CFD models of HLHS Norwood can be developed using standard angiography and echocardiographic data. The CFD analysis also revealed consistent changes in PA TAWSS, flow differential, and OSI as a function of shunt characteristics. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the application value of contrast‐enhanced transthoracic echocardiography (cTEE) in the diagnosis of patent foramen ovale (PFO) under different states of stimulation, with the goal of enhancing the accuracy and efficiency of PFO diagnosis. Methods: This research consecutively enrolled patients suspected of having PFO from October 2022 to February 2024, presenting primary clinical symptoms such as unexplained syncope, headache, dizziness, and stroke. Patients underwent standard transthoracic echocardiography (TTE) and cTEE under three different states of stimulation (resting state, coughing, and Valsalva maneuver). Based on the presence of microbubbles in the left heart and their initial appearance time, patients were classified into PFO and control groups, with further diagnostic confirmation via transesophageal echocardiography (TEE) or foramen ovale closure procedures. Results: The study results revealed significant differences between the PFO and control groups regarding age (p = 0.034) and headache symptoms (p = 0.001). In the PFO group, TTE showed a higher positivity rate both at rest and during coughing, highlighting the association between PFO and specific clinical symptoms. The number of microbubbles observed during TTE increased significantly under various stimulation states, particularly during the Valsalva maneuver (p < 0.05). This increase became more pronounced as the duration of the maneuver was extended, underscoring the differential response of PFO patients under varied physiological testing conditions, especially during prolonged Valsalva maneuvers. Conclusion: The study confirms the significant value of cTEE in diagnosing PFO under different stimulation states, particularly emphasizing the application of the Valsalva maneuver to significantly improve the sensitivity and specificity of PFO detection. Thus, incorporating cTEE examinations under various stimulation states holds significant clinical importance for enhancing the accuracy and efficiency of PFO diagnosis. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (MDS‐h) are bone marrow failure disease and difficult to distinguish merely by morphological analysis. In this study, we investigated the value of flow cytometry (FCM) in the differential diagnosis of AA and MDS‐h.We included 822 patients (626 control, 69 AA, 22 MDS‐h and 105 dilution patients) from January 2017 to December 2022 for a retrospective study. Bone marrow myeloid progenitor (MP) cell and mature lymphocytes proportions were analyzed by FCM. The ratio of MP cell proportion and mature lymphocytes proportion, MPLR, was calculated. Data were compared by Kruskal–Wallis test. Differential diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. Cutoff value was determined by the maximum Youden index.Bone marrow MP cell proportion and MPLR of MDS‐h patients were higher than AA patients. Mature lymphocytes proportion of MDS‐h patients was lower than AA patients. Area under ROC curve (AUC of ROC) of MP cell proportion, MPLR and mature lymphocytes proportion to distinguish AA from MDS‐h were 0.992, 0.988, and 0.850, respectively. Moreover, MPLR of dilution patients was higher than AA patients but lower than MDS‐h patients. The AUC of ROC curves of MPLR to distinguish MDS‐h and AA from dilution were 0.854 and 0.871, respectively.Bone marrow MP cell proportion and MPLR can effectively discriminate AA from MDS‐h with similar differential efficacy, which is higher than mature lymphocytes proportion. Moreover, MPLR can evaluate the quality of bone marrow aspirates, which would interfere with the differential diagnosis. [ABSTRACT FROM AUTHOR]

Background/Objectives: Hybrid palliation (HP) procedures for hypoplastic left heart syndrome (HLHS) are increasing. Our objective was to compare mortality and morbidity following HP and NP (Norwood palliation) procedures. Methods: Systematic review and meta-analysis of HLHS patients of peer-reviewed literature between 2000 and 2023. Mortality and/or heart transplantation in HP versus NP in the neonatal period, interstage period, and at 1, 3 and 5 years of age, and morbidity including completion of Stage II and Stage III palliation, unexpected interventions, pulmonary artery pressures, right ventricle function, neurodevelopmental outcomes and length of hospital stay were evaluated. Results: Twenty-one (meta-analysis: 16; qualitative synthesis: 5) studies evaluating 1182 HLHS patients included. HP patients had higher interstage mortality (RR = 1.61; 95% CI: 1.10–2.33; p = 0.01) and 1-year mortality (RR = 1.22; 95% CI: 1.03–1.43; p = 0.02) compared to NP patients without differences in 3- and 5-years mortality. HP procedure in high-risk HLHS patients had lower mortality (RR = 0.48; 95% CI: 0.27–0.87; p = 0.01) only in the neonatal period. HP patients underwent fewer Stage II (RR = 0.90; 95% CI: 0.81–1.00; p = 0.05) and Stage III palliation (RR = 0.78; 95% CI: 0.69–0.90; p < 0.01), had more unplanned interventions (RR = 3.38; 95% CI: 2.04–5.59; p < 0.01), and longer hospital stay after Stage I palliation (weighted mean difference = 12.88; 95% CI: 1.15–24.62; p = 0.03) compared to NP patients. Conclusions: Our study reveals that HP, compared to NP for HLHS, is associated with increased morbidity risk without an improved survival rate. [ABSTRACT FROM AUTHOR]

This research letter discusses a study that examined the impact of sex, race and ethnicity, and deprivation on the survival and completion of the Fontan pathway for children with functionally single ventricle heart disease. The study, which analyzed data from a nationally representative cohort of children in the UK, found that sociocultural and lifestyle factors may contribute to outcome disparities, despite the universal free healthcare provided by the National Health Service. The study identified certain risk factors, such as noncardiac comorbidities and increased severity of illness, that were associated with increased mortality and decreased likelihood of completing the surgery. Additionally, the study found disparities in completion rates based on sex, race and ethnicity, and area deprivation. The authors emphasize the importance of considering social determinants of health in the treatment and outcomes of children with heart disease and suggest further investigation into the impact of these disparities on long-term outcomes. [Extracted from the article]

BACKGROUND: The interstage period after discharge from stage 1 palliation carries high morbidity and mortality. The impact of social determinants of health on interstage outcomes is not well characterized. We assessed the relationship between childhood opportunity and acute interstage outcomes. METHODS: Infants discharged home after stage 1 palliation in the National Pediatric Quality Improvement Collaborative Phase II registry (2016-2022) were retrospectively reviewed. Zip code-level Childhood Opportunity Index (COI), a composite metric of 29 indicators across education, health and environment, and socioeconomic domains, was used to classify patients into 5 COI levels. Acute interstage outcomes included death or transplant listing, unplanned readmission, intensive care unit admission, unplanned catheterization, and reoperation. The association between COI level and acute interstage outcomes was assessed using logistic regression with sequential adjustment for potential confounders. RESULTS: The analysis cohort included 1837 patients from 69 centers. Birth weight (P<0.001) and proximity to a surgical center at birth (P=0.02) increased with COI level. Stage 1 length of stay decreased (P=0.001), and exclusive oral feeding rate at discharge increased (P<0.001), with higher COI level. More than 98% of patients in all COI levels were enrolled in home monitoring. Death or transplant listing occurred in 101 (5%) patients with unplanned readmission in 987 (53%), intensive care unit admission in 448 (24%), catheterization in 345 (19%), and reoperation in 83 (5%). There was no difference in the incidence or time to occurrence of any acute interstage outcome among COI levels in unadjusted or adjusted analysis. There was no interaction between race and ethnicity and childhood opportunity in acute interstage outcomes. CONCLUSIONS: Zip code COI level is associated with differences in preoperative risk factors and stage 1 palliation hospitalization characteristics. Acute interstage outcomes, although common across the spectrum of childhood opportunity, are not associated with COI level in an era of highly prevalent home monitoring programs. The role of home monitoring in mitigating disparities during the interstage period merits further investigation. [ABSTRACT FROM AUTHOR]

This article presents the findings of a study on the efficacy of posaconazole prophylaxis in patients with aplastic anemia (AA) or hypoplastic myelodysplastic syndrome (hMDS) undergoing immunosuppressive therapy (IST). The study found that posaconazole was highly effective in preventing invasive fungal infections (IFI) during IST, with only one patient (5%) experiencing an IFI. The toxicity profile of posaconazole was manageable, and the drug was well-tolerated by patients. The study concludes that posaconazole prophylaxis is efficient and safe in this patient population, and further research is needed to validate these findings. [Extracted from the article]

Neonates with congenital heart disease (CHD) have smaller brain volume at birth. High rates of placental vascular malperfusion lesions may play a role in disrupted brain development. This is a single-center retrospective cohort study of infants born between 2010 and 2019 who were diagnosed with a major cardiac defect requiring surgery in the first year of life. Doppler ultrasound RI of the middle cerebral artery (MCA) and anterior cerebral artery were calculated within the first 72 hours of life. Placentas were evaluated using a standardized approach. Over the study period, there were 52 patients with hypoplastic left heart syndrome (HLHS), 22 with single-ventricle right ventricular outflow tract obstruction (SV-RVOTO), 75 with a two-ventricle cardiac defect (2V), and 25 with transposition of the great arteries (TGA). MCA Doppler RI were significantly higher for all subgroups of CHD compared with control subjects (0.68 ± 0.11 in control subjects compared with 0.78 ± 0.13 in HLHS, P = 0.03; 0.77 ± 0.10 in SV-RVOTO, P = 0.002; 0.78 ± 0.13 in 2V, P = 0.03; and 0.80 ± 0.14 in TGA; P = 0.001) with the highest average MCA RI in the TGA group. In subgroup analyses, placental fetal vascular malperfusion in the 2V group was associated with higher MCA RI, but this relationship was not present in other subgroups, nor in regards to maternal vascular malperfusion. Major forms of CHD are associated with significantly higher cerebral artery RI postnatally, but placental vascular malperfusion lesions may not contribute to this hemodynamic adaptation. [ABSTRACT FROM AUTHOR]

OBJECTIVES Paediatric heart transplantation in children who fail multistage palliation for hypoplastic left heart syndrome is associated with challenges related to immune, clinical or anatomic risk factors. We review current outcomes and risk factors for survival following heart transplantation in this challenging patient population. METHODS The United Network for Organ Sharing transplantation database was merged with Paediatric Health Information System database to identify children who received heart transplantation following prior palliation for hypoplastic left heart syndrome. Multivariable Cox analysis of outcomes and factors affecting survival was performed. RESULTS Our cohort included 849 children between 2009 and 2021. The median age was 1044 days (interquartile range 108–3535), and the median weight was 13 kg (interquartile range 7–26). Overall survival at 10 years following heart transplantation was 71%, with most of the death being perioperative. On multivariable analysis, risk factors for survival included Black race (hazard ratio = 1.630, P  = 0.0253), blood type other than B (hazard ratio = 2.564, P  = 0.0052) and male donor gender (hazard ratio = 1.367, P  = 0.0483). Recipient age, the use of ventricular assist device or extracorporeal membrane oxygenation were not significantly associated with survival. Twenty-four patients underwent retransplantation, and 10-year freedom from retransplantation was 98%. Rejection before hospital discharge and within 1 year from transplantation was 20% and 24%, respectively, with infants having lower rejection rates. CONCLUSIONS Compared with existing literature, the number of children with prior hypoplastic left heart syndrome palliation who receive heart transplantation has increased in the current era. Survival following transplantation in this patient population is acceptable. Most of the death is perioperative. Efforts to properly support these patients before transplantation might decrease early mortality and improve overall survival. [ABSTRACT FROM AUTHOR]

Objective: Image quality of fetal echocardiography (FE) has improved in the recent era, but few recent studies have reported the accuracy of FE, specifically in single ventricle (SV) congenital heart disease (CHD). This study aimed to assess the ability of FE to correctly predict SV‐CHD postnatal anatomy and physiology in a contemporary cohort. Methods: The contemporary clinical reports of patients with SV‐CHD, in which FE was performed between July 2017 and July 2021, were compared with postnatal echocardiograms from a formal quality assurance program. SV fetuses were grouped by anatomical subtype. Diagnostic errors were designated as major if the error would have caused significant alteration in parental counseling or postnatal management. The remaining errors were classified as minor. Physiological discrepancies, including prostaglandin‐E (PGE) dependency, atrioventricular valve regurgitation (AVVR), pulmonary venous obstruction and restrictive atrial septum (RAS), were assessed by chart review of the postnatal course. Results: A total of 119 subjects were analyzed. SV subtypes in the cohort included hypoplastic left heart syndrome (HLHS) (n = 68), tricuspid atresia (n = 16), double‐inlet left ventricle (n = 12), unbalanced atrioventricular canal (UAVC) (n = 11), heterotaxy (n = 9) and other (n = 3). The rate of major anatomical and physiological errors was low (n = 6 (5.0%)). A higher proportion of minor errors was noted in HLHS and tricuspid atresia, but the differences were not statistically significant. Physiological discrepancies were uncommon, with three major discrepancies, including underestimation of the degree of venous obstruction in one non‐HLHS fetus with total anomalous pulmonary venous return, overestimation of RAS in one HLHS fetus and incorrect prediction of PGE dependency in one case false‐negative for pulmonary blood flow. No discrepancy in degree of AVVR or RAS affected postnatal care. Minor physiological discrepancies included two false‐positive predictions of PGE dependency with one false‐positive for ductal‐dependent systemic flow and one false‐positive for pulmonary blood flow. Conclusions: In this contemporary review of FE at our center, there was high accuracy in describing anatomical and physiological findings in SV‐CHD. Major physiological discrepancies were uncommon but included important cases of false‐negative prediction of PGE dependency and underestimation of obstruction of total anomalous pulmonary venous return. These data can inform more accurate counseling of families with SV‐CHD fetuses and guide diagnostic improvement efforts. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Hybrid interventions in congenital heart disease (CHD) embody the inherent collaboration between congenital interventional cardiology and cardiothoracic surgery. Hybrid approaches to complex and common lesions provide the opportunity to circumvent the limitations of patient size, vascular access, severity of illness, and anatomy that would otherwise be prohibitive to surgical and percutaneous techniques alone. This review describes several important hybrid approaches to interventions in CHD. [ABSTRACT FROM AUTHOR]

This article will detail Dr. James Tweddell's operative technique and considerations for 26 all three stages of SVP in patients with HLHS. This will include the Norwood Procedure with 27 Right-Ventricle-to-Pulmonary-Artery Conduit (Sano Modification), Bidirectional Glenn 28 (Superior Cavopulmonary Connection), and Extracardiac, Fenestrated Fontan Completion (Total 29 Cavopulmonary Connection). These techniques are the culmination of over 20 years of experience 30 and represent the final techniques he employed at both Children's Hospital of Wisconsin and 31 Cincinnati Children's Hospital Medical Center. [ABSTRACT FROM AUTHOR]

IMPORTANCE: Extubation failure (EF) after pediatric cardiac surgery is associated with increased morbidity and mortality. OBJECTIVES: We sought to describe the risk factors associated with early (< 48 hr) and late (48 hr ≤ 168 hr) EF after pediatric cardiac surgery and the clinical implications of these two types of EF. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study using prospectively collected clinical data for the Pediatric Cardiac Critical Care Consortium (PC4) Registry. Pediatric patients undergoing Society of Thoracic Surgeons benchmark operation or heart transplant between 2013 and 2018 available in the PC4 Registry were included. MAIN OUTCOMES AND MEASURES: We analyzed demographics and risk factors associated with EFs (primary outcome) including by type of surgery. We identified potentially modifiable risk factors. Clinical outcomes of mortality and length of stay (LOS) were reported. RESULTS: Overall 18,278 extubations were analyzed. Unplanned extubations were excluded from the analysis. The rate of early EF was 5.2% (948) and late EF was 2.5% (461). Cardiopulmonary bypass time, ventilator duration, airway anomaly, genetic abnormalities, pleural effusion, and diaphragm paralysis contributed to both early and late EF. Extubation during day remote from shift change and nasotracheal route of initial intubation was associated with decreased risk of early EF. Extubation in the operating room was associated with an increased risk of early EF but with decreased risk of late EF. Across all operations except arterial switch, EF portrayed an increased burden of LOS and mortality. CONCLUSION AND RELEVANCE: Both early and late EF are associated with significant increase in LOS and mortality. Study provides potential benchmarking data by type of surgery. Modifiable risk factors such as route of intubation, time of extubation as well as treatment of potential contributors such as diaphragm paralysis or pleural effusion can serve as focus areas for reducing EFs.

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart defect (CHD) characterized by a spectrum of underdeveloped left-sided cardiac structures. It is a serious defect and warrants either 3-staged surgical palliation or a heart transplant. Despite numerous surgical advancements, long-term outcomes remain challenging and still have significant morbidity and mortality. There have been notable advancements in stem cell therapy for HLHS, including developments in diverse stem cell origins and methods of administration. Clinical trials have shown safety and potential benefits, including improved ventricular function, reduced heart failure, and fewer adverse events. Younger myocardium seems particularly receptive to stem cell signals, suggesting the importance of early intervention. This review explores the potential of emerging stem cell-based therapies as an adjunctive approach to improve the outcomes for HLHS patients.

BackgroundCharacterization of brain injury and neurodevelopmental (ND) outcomes in critical congenital heart disease (cCHD) has primarily focused on hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA). This study reports brain injury and ND outcomes among patients with heterogeneous cCHD diagnoses beyond HLHS and TGA.MethodsThis prospective cohort study included infants with HLHS, TGA, or heterogenous "Other cCHD" including left- or right-sided obstructive lesions, anomalous pulmonary venous return, and truncus arteriosus. Brain injury on perioperative brain MRI and ND outcomes on the Bayley-II at 30 months were compared.ResultsA total of 218 participants were included (HLHS = 60; TGA = 118; "Other cCHD" = 40, including 8 with genetic syndromes). Pre-operative (n = 209) and post-operative (n = 189) MRI showed similarly high brain injury rates across groups, regardless of cardiopulmonary bypass exposure. At 30 months, participants with "Other cCHD" had lower cognitive scores (p = 0.035) compared to those with HLHS and TGA, though worse ND outcome in this group was driven by those with genetic disorders.ConclusionsFrequency of brain injury and neurodevelopmental delay among patients with "Other cCHD" is similar to those with HLHS or TGA. Patients with all cCHD lesions are at risk for impaired outcomes; developmental and genetic screening is indicated.ImpactThis study adds to literature on risk of brain injury in patients with critical congenital heart disease (cCHD) diagnoses other than hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA), a heterogenous cohort of patients that has often been excluded from imaging studies. Children with cCHD beyond HLHS and TGA have similarly high rates of acquired brain injury. The high rate of neurodevelopmental impairment in this heterogenous group of cCHD diagnoses beyond HLHS and TGA is primarily driven by patients with comorbid genetic syndromes such as 22q11.2 deletion syndrome.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with a likely oligogenic etiology, but our understanding of the genetic complexities and pathogenic mechanisms leading to HLHS is limited. We performed whole genome sequencing (WGS) on 183 HLHS patient-parent trios to identify candidate genes, which were functionally tested in the Drosophila heart model. Bioinformatic analysis of WGS data from an index family of a HLHS proband born to consanguineous parents prioritized 9 candidate genes with rare, predicted damaging homozygous variants. Of them, cardiac-specific knockdown (KD) of mitochondrial MICOS complex subunit dCHCHD3/6 resulted in drastically compromised heart contractility, diminished levels of sarcomeric actin and myosin, reduced cardiac ATP levels, and mitochondrial fission-fusion defects. These defects were similar to those inflicted by cardiac KD of ATP synthase subunits of the electron transport chain (ETC), consistent with the MICOS complexs role in maintaining cristae morphology and ETC assembly. Five additional HLHS probands harbored rare, predicted damaging variants in CHCHD3 or CHCHD6. Hypothesizing an oligogenic basis for HLHS, we tested 60 additional prioritized candidate genes from these patients for genetic interactions with CHCHD3/6 in sensitized fly hearts. Moderate KD of CHCHD3/6 in combination with Cdk12 (activator of RNA polymerase II), RNF149 (goliath, E3 ubiquitin ligase), or SPTBN1 (β-Spectrin, scaffolding protein) caused synergistic heart defects, suggesting the likely involvement of diverse pathways in HLHS. Further elucidation of novel candidate genes and genetic interactions of potentially disease-contributing pathways is expected to lead to a better understanding of HLHS and other CHDs.

Congenital heart anomalies (CHA) represent a substantial risk to neonates, with 28% to 48% of cases resulting in life-threatening conditions. Consequently, careful prenatal screening is crucial for effective management. Within the spectrum of 18 CHA types, identifying the irregularities in heart morphology, notably the underdeveloped left heart chamber, poses a significant challenge. Hypoplastic Left Heart Syndrome (HLHS), an infrequent yet critical CHA demands diagnosis between the 17th and 21st week of growth. Despite the efficacy of ultrasound imaging, the diagnosis remains intricate due to speckle noise and the complex nature of heart chamber appearances. Selecting an accurate pre-processing algorithm is crucial, and the Fuzzy-based Maximum Likelihood Estimation Technique (FMLET) stands as a pivotal choice. Among the vital parameters for manual diagnosis from ultrasound images, the Right Ventricular Left Ventricular Ratio (RVLVR) and the Cardiac Thoracic Ratio (CTR) play a prominent role. Employing morphological operations such as opening, closing, thinning, and thickening facilitates the extraction of diagnostically crucial features embedded within the images. The development of a Computer-Aided Decision Support (CADS) system, integrating an Adaptive Neuro Fuzzy Classifier (ANFC) proves to be instrumental. ANFC stands out as a better classifier and demonstrates self-learning capabilities similar to that of experts, resulting in a higher diagnostic accuracy rate. The presented Computer-Aided Diagnostic System (CADS) exhibited a notable diagnostic accuracy of 91%, supported by a standardized Area Under the Receiver Operating Characteristic (ROC) curve of 0.92. These results emphasize the system's robustness and effectiveness in diagnosing prenatal CHA, particularly HLHS. [ABSTRACT FROM AUTHOR]

Introduction: Objective: Prenatal detection of congenital heart disease (CHD) using fetal echocardiography (FE) helps in early diagnosis leading to prompt management and treatment. FE provides a highly accurate non-invasive modality to improve the survival or quality of life of CHD patients. The aim of this study was to evaluate the antenatal detection of CHD by FE and compare it with the results of postnatal echocardiography. Methods: A prospective cohort study of pregnant women referred to a tertiary center Imam-Reza Hospital, Mashhad, Iran, for performing FE in the hands of an experienced pediatric cardiologist between 2012 and 2021. Cardiac echocardiography was performed by GE Vivid 7 color Doppler and Mindray Resona 7 color Doppler with convex probe 5-7 megahertz during late first trimester or early second trimester and after birth until 2 months later. Data were analyzed using SPSS and MedCalc software, and agreement was assessed using kappa. Results: Out of 261 studied fetuses, 101 normal cases were detected in full agreement with postnatal echo diagnosis. Acceptable diagnosis was found for septal defects; VSDs were highly statistically detected (sensitivity= 90%, specificity= 93%). Complex CHDs were found to be the most accurate prenatal diagnosis. Right arch anomalies, aortic stenosis, hypoplastic left heart syndrome and cardiac masses were perfectly acceptable, but detection of coarctation of the aorta faced with over-diagnosis. Prenatally diagnosed arrhythmias without structural defects, mostly premature beats, shifted to normal postnatal echo. Conclusion: FE is a safe and sensitive modality in prenatal diagnosis of CHDs. The study showed the effectiveness accuracy of early first trimester; also complete detection in both sides of the defect spectrum. [ABSTRACT FROM AUTHOR]

OBJECTIVES End-stage congenital heart disease (CHD) in children with heterotaxy syndrome might necessitate a heart transplant (HTx). An HTx in heterotaxy patients can be associated with several technical (e.g. redo, systemic/pulmonary-venous/situs anomalies, pulmonary artery reconstruction) and extra-cardiac (e.g. ciliary dyskinesia, infections, gastrointestinal) challenges. Our goal was to determine if heterotaxy syndrome is associated with increased early or late transplant risks. METHODS The United Network for Organ Sharing transplant database was merged with the Paediatric Health Information System administrative database to identify children with heterotaxy who received an HTx. Characteristics and outcomes were compared between children with heterotaxy and contemporaneous non-heterotaxy congenital and non-congenital cardiomyopathy control groups. RESULTS After we merged the databases, we divided our cohort of 1122 patients into 3 groups: the heterotaxy (n  = 143), group the non-heterotaxy congenital (n  = 428) group and the cardiomyopathy (n  = 551) group. There were differences in the characteristics between the 3 groups, with the heterotaxy group being comparable to the non-heterotaxy congenital group. The waiting list duration was longer for the heterotaxy than for the non-heterotaxy congenital and cardiomyopathy groups (91 vs 63 vs 56 days, P  < 0.001). Early post-transplant complications were similar for all groups except for operative mortality, which was 1% for the cardiomyopathy and 4% for the heterotaxy and non-heterotaxy congenital groups (P  < 0.001). The post-transplant hospital stay was shorter for the cardiomyopathy (57 days) compared to the non-heterotaxy congenital (99 days) and heterotaxy (89 days) groups (P  < 0.001). Whereas rejection prior to discharge was comparable between the heterotaxy and the CHD groups, it was higher at 1 year for the heterotaxy (22%) than for the non-heterotaxy congenital (19%) and cardiomyopathy (13%) groups (P  < 0.001). Survival at 5 years was superior for the cardiomyopathy (87%) compared to the heterotaxy (69%) and non-heterotaxy congenital groups (78%) (P  < 0.001). For the heterotaxy group, no risk factors affecting survival were identified on multivariable analysis. CONCLUSIONS Regardless of the complexity, an HTx in selected children with heterotaxy is associated with good mid-term outcomes. Despite early results that are comparable to those of other patients with CHD, the increasing rejection rate at 1 year and the relatively accelerated attrition at mid-term warrant further follow-up. Due to database limitations in defining morphologic and surgical details, further work is warranted to delineate anatomical and surgical variables that could affect survival. [ABSTRACT FROM AUTHOR]

Cardiac dysfunction is associated with mortality in children with hypoplastic left heart syndrome (HLHS). We evaluated the ability of qualitative and quantitative RV functional parameters to predict outcomes in HLHS patients. In this retrospective, single-center study, echocardiograms from 3 timepoints (pre-stage 1 palliation, 4–8 weeks post-stage 1 palliation, and pre-Glenn) were analyzed in infants with HLHS. Patients were stratified into two groups based on outcome of transplant-free survival post-Glenn (survivors) versus mortality or transplantation prior to Fontan (non-survivors). Images were retrospectively reviewed to obtain RV global longitudinal strain (RVGLS), RV-free wall strain (RVFWS), fractional area change (FAC), tricuspid annular systolic plane excursion (TAPSE), tissue motion annular displacement of the tricuspid valve (TMAD-TV) and qualitative systolic function assessment during the predetermined timepoints. An equal variance t-test and chi-square were used to determine significant differences and ROC curve analysis was performed to derive optimal cutoff values to predict mortality/transplant. A total of 47 patients met inclusion criteria, of which, 21 patients met composite endpoint. There were no significant differences in any RV functional parameter during the pre- or post-stage 1 palliation timepoints. The absolute values of RVFWS, RVGLS, and TMAD-TV were significantly greater in survivors than non-survivors during the pre-Glenn timepoint. A pre-Glenn RVGLS > −15.6 (AUC 0.79), RVFWS > −18.6 (AUC 0.75), and TMAD-TV < 12.6% (AUC 0.82) were sensitive and specific for predicting death or need for transplantation prior to Fontan completion. RVGLS, RVFWS, and TMAD-TV may help identify higher-risk HLHS patients during the interstage period. [ABSTRACT FROM AUTHOR]

As a strategy for the primary Norwood operation, the right ventricular–pulmonary artery shunt is associated with satisfactory early outcome. However, use of this shunt after bilateral pulmonary artery banding remains controversial. This study compared the operative outcomes and late hemodynamics in patients who underwent the Norwood operation, preceded by bilateral pulmonary artery banding, with a right ventricular–pulmonary artery shunt or with bidirectional Glenn anastomosis (comprehensive stage II strategy). We retrospectively reviewed 38 patients who underwent the Norwood operation preceded by bilateral pulmonary artery banding between 2004 and 2017. Of these, 17 underwent the Norwood operation with a right ventricular–pulmonary artery shunt (Group S), whereas 21 underwent the comprehensive stage II strategy (Group G). 5 years after the Norwood operation, 10 (60%) and 17 (81%) patients in Group S and Group G, respectively, underwent the Fontan procedure. Group S showed significantly lower pressure in the superior vena cava after bidirectional Glenn anastomosis than Group G (13 ± 2 mmHg vs. 18 ± 3 mmHg; p < 0.01), but pressures were similar after the Fontan procedure. The right ventricular end-diastolic volume at 1 year post-Fontan procedure was significantly higher in Group S than in Group G (142 ± 41% vs. 91 ± 28%; p < 0.01). In terms of early outcomes, the Norwood operation with a right ventricular–pulmonary artery shunt enabled low pressure in the superior vena cava, but in the long term, this shunt adversely influenced the right ventricular volume. [ABSTRACT FROM AUTHOR]