Dicyanopyridine derivatives: One-pot preparation, ACQ-to-AIE transformation, light-conversion quality and photostability.

Low cost and strong fluorescence emission are two important guarantees for luminogens used as light conversion agents. By one-pot multicomponent approach and inexpensive starting materials, three dicyanopyridine (DP) derivatives named as DCP (2-amino-6-methoxy-4-phenylpyridine-3,5-dicarbonitrile), DCO (2-amino-6-methoxy-4-(4-methoxyphenyl) pyridine-3,5-dicarbonitrile) and DCC (2-amino-4-(4-cyanophenyl)-6-methoxypyridine-3,5-dicarbonitrile) were designed and synthesized. Meanwhile, the ACQ-to-AIE transformation was successfully realized by altering substituent groups rather than traditional rotor-stator theory. Based on crystal analysis and theoretical calculations, the ACQ-to-AIE transformation is attributed to the tunable stacking modes and intermolecular weak interactions. Owing to matched fluorescence emission, low lost, high yield, and AIE activity, DCC is used as light conversion agents and doped in EVA matrix. The light conversion quality confirms that DCC can not only convert ultraviolet light, but also significantly improve the transmittance of 25 %/40 % EVA, whose photosynthetic photon flux density at 400-500 nm and 600-700 nm increased to 30.67 %/30.21 % and 25.37 %/37.82 % of the blank film, respectively. After 20 h of UV irradiation (365 nm, 40 W), the fluorescence intensities of DCC films can maintain 92 % of the initial values, indicating good photostability in the doping films. This work not only provides an excellent and low-cost light conversion agent, but also has important significance for ACQ-to-AIE transformation of luminogens.

The activation of RARα prevents surgery-induced cognitive impairments via the inhibition of neuroinflammation and the restoration of synaptic proteins in elderly mice.

Post-operative cognitive dysfunction (POCD) is a multi-etiological symptom mainly occurred in elderly people after surgery. The activation of retinoic acid receptor α (RARα), a transcriptional factor, was previously predicated to be negatively associated with the occurrence of POCD. However, the mechanisms underlying anti-POCD effects of RARα were still unclear. In this study, AM580, a selective agonist of RARα, and all-trans-retinoic acid (ATRA), a pan agonist of RAR, significantly alleviated cognitive dysfunction and increased the expression of RARα in elderly mice after surgery, which was decreased by RO41-5253, an antagonist of RARα. A bioinformatic study further predicted that the activation of RARα might produce anti-POCD effects via the restoration of synaptic proteins. Both agonists inhibited the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and the phosphorylation of nuclear factorkappa-B (NF-κB), leading to the prevention of microglial over-activation and pro-inflammatory cytokines secretion in the hippocampal regions of elderly mice after surgery. Moreover, AM580 and ATRA increased the expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95), and the phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP-response element binding protein (CREB). All these results suggested that the activation of RARα prevented surgery-induced cognitive impairments via the inhibition of neuroinflammation by the reduction of the TLR4/Myd88/NF-κB pathway and the restoration of synaptic proteins by the activation of the BDNF/ERK/CREB pathway, providing a further support that RARα could be developed as a therapeutic target for POCD.

An economical single-shot pulse picker without nonlinear effect and dispersion.

An economical and stable single-shot pulse picker design without dispersion, nonlinear effect, and limitation on wavelength is proposed. This design is composed of a periodic pulse blocker (PPB), a control unit, and a mechanical shutter. It has successfully been applied to the commercial high-fluence femtosecond laser with 11-mm beam diameter, 2-mJ pulse energy, and 1-kHz repetition rate. Significantly, by incorporating commercial optical choppers equipped with custom-designed chopper blades in the PPB, this design can accommodate lasers with fluences reaching 610 mJ/cm2 and the standard 1 kHz repetition rate typical of high-fluence lasers. Furthermore, the proposed design provides a cost-effective substitute compared to using electro-optic modulators or acousto-optic modulators.

The Effect of Udenafil on Heart Rate and Blood Pressure in Adolescents With the Fontan Circulation.

The Fontan Udenafil Exercise Longitudinal (FUEL) trial showed that treatment with udenafil was associated with improved exercise performance at the ventilatory anaerobic threshold in children with Fontan physiology. However, it is not known how the initiation of phosphodiesterase 5 inhibitor therapy affects heart rate and blood pressure in this population. These data may help inform patient selection and monitoring after the initiation of udenafil therapy. The purpose of this study is to evaluate the effects of udenafil on vital signs in the cohort of patients enrolled in the FUEL trial. This international, multicenter, randomized, double-blind, placebo-controlled trial of udenafil included adolescents with single ventricle congenital heart disease who had undergone Fontan palliation. Changes in vital signs (heart rate [HR], systolic [SBP] and diastolic blood pressure [DBP]) were compared both to subject baseline and between the treatment and the placebo groups. Additional exploratory analyses were performed to evaluate changes in vital signs for prespecified subpopulations believed to be most sensitive to udenafil initiation. Baseline characteristics were similar between the treatment and placebo cohorts (n = 200 for each). The groups demonstrated a decrease in HR, SBP, and DBP 2 hours after drug/placebo administration, except SBP in the placebo group. There was an increase in SBP from baseline to after 6-min walk test in the treatment and placebo groups, and the treatment group showed an increase in HR (87.4 ± 15.0 to 93.1 ± 19.4 beats/min, p <0.01) after exercise. When comparing changes from baseline to the 26-week study visit, small decreases in both SBP (-1.9 ± 12.3 mm Hg, p = 0.03) and DBP (-3.0 ± 9.6 mm Hg, p <0.01) were seen in the treatment group. There were no clinically significant differences between treatment and placebo group in change in HR or blood pressure in the youngest age quartile, lightest weight quartile, or those on afterload-reducing agents. In conclusion, initiation of treatment with udenafil in patients with Fontan circulation was not associated with clinically significant changes in vital signs, implying that for patients similar to those enrolled in the FUEL trial, udenafil can be started without the requirement for additional monitoring after initial administration.

New insights into brominated epoxy resin type WPCBs pyrolysis mechanisms: Integrated experimental and DFT simulation studies.

Pyrolysis is a recycling technology for waste circuit boards (WPCBs) with a wide range of applications. In this research, the brominated epoxy resin (BER) type WPCBs were taken as the research object, and the optimal pyrolysis process parameters were determined. Combined with experiments and density functional theory (DFT) calculations, the pyrolysis gaseous generation pattern and product distribution of BER type WPCBs were analyzed, and the generation mechanism of phenol, bromide and other pyrolysis products was investigated in depth. The results of the study showed that the pyrolysis rate of WPCBs exceeded 95 % under optimal reaction conditions. In the initial phase of the pyrolysis of WPCBs, the BER's CO bonds and a portion of Ph-Br bonds will be broken, leading to the production of intermediates such propylene oxide, bisphenol A, isopropyl alcohol, tetrabromobisphenol A and HBr. Among them, propylene oxide can generate ethylene oxide through free radical reaction. In the second stage, intermediates such as bisphenol A undergo homolytic cleavage and radical addition to form phenols, bromides, alcohols, ketones and other pyrolysis products.

Fucoxanthin, a marine derived carotenoid, attenuates surgery-induced cognitive impairments via activating Akt and ERK pathways in aged mice.

BACKGROUND: Fucoxanthin is the most abundant marine carotenoid derived from brown seaweeds, possesses antioxidant, anti-inflammatory, and neuroprotective properties, and might be benefit for the treatment of neurological disorders. Post-operative cognitive dysfunction (POCD) is a neurological symptom with learning and memory impairments, mainly affecting the elderly after surgery. However, there is no effective treatments for this symptom. PURPOSES: In this study, we evaluated the neuroprotective effects of fucoxanthin against POCD in aged mice after surgery. STUDY DESIGN AND METHODS: The animal model of POCD was established in 12 - 14 month aged mice with a laparotomy. Curcumin was used as a positive control. The beneficial effects of fucoxanthin on POCD was analyzed by behavioral tests. Pro-inflammatory cytokines were measured by Enzyme-linked Immunosorbent Assay (ELISA). And the expressions of key proteins in the Akt and ERK signaling pathways were analyzed by Western blotting analysis. The morphology of microglial cells and astrocytes was explored by immunohistochemical staining. The activity of antioxidant superoxide dismutase (SOD) and catalase (CAT) were measured by anti-oxidative enzyme activity assays. RESULTS: Fucoxanthin at 100 - 200 mg/kg significantly attenuated cognitive dysfunction, with a similar potency as curcumin, in aged mice after surgery. In addition, fucoxanthin and curcumin significantly increased the expression of pAkt, prevented the activation of microglial cells and astrocytes, and inhibited the secretion of pro-inflammatory interleukin-1ß (IL - 1ß) and tumor necrosis factor-α (TNF-α). Furthermore, fucoxanthin and curcumin elevated the ERK pathway and potently increased the activity of antioxidant enzymes. Most importantly, U0126, an inhibitor of the ERK pathway, and wortmannin, an inhibitor of the Akt pathway, significantly abolished the cognitive-enhancing effects, as well as the inhibition of neuroinflammation and the reduction of oxidative stress, induced by fucoxanthin in aged mice after surgery. CONCLUSION: Fucoxanthin might be developed as a functional food or drug for the treatment of POCD by inhibiting neuroinflammation and enhancing antioxidant capacity via the activation of the Akt and ERK signaling pathways.

PANoptosis-based molecular subtyping and HPAN-index predicts therapeutic response and survival in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a highly prevalent and fatal cancer. The role of PANoptosis, a novel form of programmed cell death, in HCC is yet to be fully understood. This study focuses on identifying and analyzing PANoptosis-associated differentially expressed genes in HCC (HPAN_DEGs), aiming to enhance our understanding of HCC pathogenesis and potential treatment strategies. Methods: We analyzed HCC differentially expressed genes from TCGA and IGCG databases and mapped them to the PANoptosis gene set, identifying 69 HPAN_DEGs. These genes underwent enrichment analyses, and consensus clustering analysis was used to determine three distinct HCC subgroups based on their expression profiles. The immune characteristics and mutation landscape of these subgroups were evaluated, and drug sensitivity was predicted using the HPAN-index and relevant databases. Results: The HPAN_DEGs were mainly enriched in pathways associated with the cell cycle, DNA damage, Drug metabolism, Cytokines, and Immune receptors. We identified three HCC subtypes (Cluster_1, SFN+PDK4-; Cluster_2, SFN-PDK4+; Cluster_3, SFN/PDK4 intermediate expression) based on the expression profiles of the 69 HPAN_DEGs. These subtypes exhibited distinct clinical outcomes, immune characteristics, and mutation landscapes. The HPAN-index, generated by machine learning using the expression levels of 69 HPAN_DEGs, was identified as an independent prognostic factor for HCC. Moreover, the high HPAN-index group exhibited a high response to immunotherapy, while the low HPAN-index group showed sensitivity to small molecule targeted drugs. Notably, we observed that the YWHAB gene plays a significant role in Sorafenib resistance. Conclusion: This study identified 69 HPAN_DEGs crucial to tumor growth, immune infiltration, and drug resistance in HCC. Additionally, we discovered three distinct HCC subtypes and constructed an HPAN-index to predict immunotherapeutic response and drug sensitivity. Our findings underscore the role of YWHAB in Sorafenib resistance, presenting valuable insights for personalized therapeutic strategy development in HCC.

The Fontan Udenafil Exercise Longitudinal Trial: Subgroup Analysis.

The Pediatric Heart Network's Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT02741115) demonstrated improvements in some measures of exercise capacity and in the myocardial performance index following 6 months of treatment with udenafil (87.5 mg twice daily). In this post hoc analysis, we evaluate whether subgroups within the population experienced a differential effect on exercise performance in response to treatment. The effect of udenafil on exercise was evaluated within subgroups defined by baseline characteristics, including peak oxygen consumption (VO2), serum brain-type natriuretic peptide level, weight, race, gender, and ventricular morphology. Differences among subgroups were evaluated using ANCOVA modeling with fixed factors for treatment arm and subgroup and the interaction between treatment arm and subgroup. Within-subgroup analyses demonstrated trends toward quantitative improvements in peak VO2, work rate at the ventilatory anaerobic threshold (VAT), VO2 at VAT, and ventilatory efficiency (VE/VCO2) for those randomized to udenafil compared to placebo in nearly all subgroups. There was no identified differential response to udenafil based on baseline peak VO2, baseline BNP level, weight, race and ethnicity, gender, or ventricular morphology, although participants in the lowest tertile of baseline peak VO2 trended toward larger improvements. The absence of a differential response across subgroups in response to treatment with udenafil suggests that the treatment benefit may not be restricted to specific sub-populations. Further work is warranted to confirm the potential benefit of udenafil and to evaluate the long-term tolerability and safety of treatment and to determine the impact of udenafil on the development of other morbidities related to the Fontan circulation.Trial Registration NCT0274115.

Uncovering the mechanism of Kang-ai injection for treating intrahepatic cholangiocarcinoma based on network pharmacology, molecular docking, and in vitro validation.

Objective: Kang-ai injection (KAI) has been a popular adjuvant treatment for solid tumors, but its anti-tumor mechanism in intrahepatic cholangiocarcinoma (ICC) remains poorly understood. This study applied a network pharmacology-based approach to unveil KAI's anti-tumor activity, key targets, and potential pharmacological mechanism in ICC by integrating molecular docking and in vitro validation. Methods: The KAI-compound-target-ICC network was constructed to depict the connections between active KAI compounds and ICC-related targets based on the available data sources. The crucial ingredients, potential targets, and signaling pathways were screened using GO, KEGG enrichment analysis, and the PPI network. Molecular docking was performed to visualize the interactions between hub targets and components. In vitro experiments were carried out to validate the findings. Results: Among the 87 active components of KAI and 80 KAI-ICC-related targets, bioinformatics analysis identified quercetin as a possible candidate. GO and KEGG enrichment analysis indicated that the PI3K-AKT signaling pathway might be essential in ICC pharmacotherapy. The PPI network and its sub-networks screened 10 core target genes, including AKT1 and IL1ß. Molecular docking results showed stable binding between AKT1 and IL1ß with KAI active ingredients. The in vitro experiments confirmed that KAI might suppress the proliferation of ICC cell lines by inhibiting the PI3K/AKT signaling pathway, consistent with the network pharmacology approach and molecular docking predictions. Conclusion: The study sheds light on KAI's biological activity, potential targets, and molecular mechanisms in treating ICC and provides a promising strategy for understanding the scientific basis and therapeutic mechanisms of herbal treatments for ICC. This research has important implications for developing new, targeted therapies for ICC and highlights the importance of network pharmacology-based approaches in investigating complex herbal formulations.

Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants.

BACKGROUND: The FUEL trial (Fontan Udenafil Exercise Longitudinal) demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle function in this cohort has not been studied. METHODS: The 400 enrolled participants were randomized 1:1 to udenafil or placebo. Protocol echocardiograms were obtained at baseline and 26 weeks after initiation of udenafil/placebo. Linear regression compared change from baseline indices of single ventricle systolic, diastolic and global function, atrioventricular valve regurgitation, and mean Fontan fenestration gradient in the udenafil cohort versus placebo, controlling for ventricular morphology (left ventricle versus right ventricle/other) and baseline value. RESULTS: The udenafil participants (n=191) had significantly improved between baseline and 26 weeks visits compared to placebo participants (n=195) in myocardial performance index (P=0.03, adjusted mean difference [SE] of changes between groups -0.03[0.01]), atrioventricular valve inflow peak E (P=0.009, 3.95 [1.50]), and A velocities (P=0.034, 3.46 [1.62]), and annular Doppler tissue imaging-derived peak e' velocity (P=0.008, 0.60[0.23]). There were no significant differences in change in single ventricle size, systolic function, atrioventricular valve regurgitation severity, or mean fenestration gradient. Participants with a dominant left ventricle had significantly more favorable baseline values of indices of single ventricle size and function (lower volumes and areas, E/e' ratio, systolic:diastolic time and atrioventricular valve regurgitation, and higher annular s' and e' velocity). CONCLUSIONS: FUEL participants who received udenafil demonstrated a statistically significant improvement in some global and diastolic echo indices. Although small, the changes in diastolic function suggest improvement in pulmonary venous return and/or augmented ventricular compliance, which may help explain improved exercise performance in that cohort. REGISTRATION: URL: https://clinicaltrials.gov; Unique Identifier: NCT02741115.

Six-Year Neurodevelopmental Outcomes for Children With Single-Ventricle Physiology.

OBJECTIVES: To determine if neurodevelopmental deficits in children with single-ventricle physiology change with age and early developmental scores predict 6-year outcomes. METHODS: In the Single Ventricle Reconstruction Trial, Bayley Scales of Infant Development, Second Edition, were administered at 14 months of age, and parents completed the Behavior Assessment System for Children, Second Edition (BASC-2) annually from the ages of 2 to 6 years. Scores were classified as average, at risk, or impaired. We calculated sensitivities, specificities, and positive and negative predictive values of earlier tests on 6-year outcomes. RESULTS: Of 291 eligible participants, 244 (84%) completed the BASC-2 at 6 years; more Single Ventricle Reconstruction participants than expected on the basis of normative data scored at risk or impaired on the BASC-2 Adaptive Skills Index at that evaluation (28.7% vs 15.9%; P < .001). Children with Adaptive Skills Composite scores <2 SD below the mean at the age of 6 were more likely to have had delayed development at 14 months, particularly on the Psychomotor Development Index (sensitivity of 79%). However, the positive predictive value of the 14-month Mental Development Index and Psychomotor Development Index for 6-year BASC-2 Adaptive Scores was low (44% and 36%, respectively). Adaptive Skills Composite score impairments at the age of 6 were poorly predicted by using earlier BASC-2 assessments, with low sensitivities at the ages of 3 (37%), 4 (48%), and 5 years (55%). CONCLUSIONS: Many children with hypoplastic left heart syndrome who have low adaptive skills at the age of 6 years will not be identified by screening at earlier ages. With our findings, we highlight the importance of serial evaluations for children with critical congenital heart disease throughout development.

Behavior and Quality of Life at 6 Years for Children With Hypoplastic Left Heart Syndrome.

OBJECTIVES: We measured behavioral, quality of life (QoL), and functional status outcomes for 6-year-old children with hypoplastic left heart syndrome enrolled in the Single Ventricle Reconstruction Trial. We sought to compare these outcomes with those in the normative population and to analyze risk factors for worse outcomes within the single-ventricle group. METHODS: Parent-response instruments included the Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) (primary outcome), Behavior Assessment System for Children 2, Pediatric Quality of Life Inventory 4.0, and other measures of QoL and functional status. We compared subjects with those in the normative sample using 1-sample Wilcoxon rank tests and assessed outcome predictors using multivariable regression. RESULTS: Of 325 eligible patients, 250 (77%) participated. Compared with population norms, participants had lower scores on the Vineland-II motor skills domain (90 ± 17 vs 100 ± 15; P < .001), with 11% scoring >2 SDs below the normative mean. On nearly all major domains, more study subjects (3.3%-19.7%) scored outside the normal range than anticipated for the general population. Independent risk factors for lower Vineland-II scores included perioperative extracorporeal membrane oxygenation, male sex, use of regional cerebral perfusion, catheterization after stage 2 operation, visual problems, seizure history, and more complications after 2 years (R 2 = 0.32). Independent predictors of worse Behavior Assessment System for Children 2 (R 2 = 0.07-0.20) and Pediatric Quality of Life Inventory 4.0 (R 2 = 0.17-0.25) domain scores also included sociodemographic factors and measures of morbidity and/or greater course complexity. CONCLUSIONS: At 6 years, children with hypoplastic left heart syndrome had difficulty in areas of adaptive behavior, behavioral symptoms, QoL, and functional status. Principal risks for adverse outcomes include sociodemographic factors and measures of greater course complexity. However, models reveal less than one-third of outcome variance.

Gestational Age, Birth Weight, and Outcomes Six Years After the Norwood Procedure.

BACKGROUND: Preterm delivery and low birth weight (LBW) are generally associated with worse outcomes in hypoplastic left heart syndrome (HLHS), but an individual preterm or small neonate may do well. We sought to explore the interactions between gestational age, birth weight, and birth weight for gestational age with intermediate outcomes in HLHS. METHODS: We analyzed survival, growth, neurodevelopment, length of stay, and complications to age 6 years in subjects with HLHS from the Single Ventricle Reconstruction trial. Univariate and multivariable survival and regression analyses examined the effects and interactions of LBW (<2500 g), weight for gestational age, and gestational age category. RESULTS: Early-term delivery (n = 234) was more common than term (n = 219) delivery. Small for gestational age (SGA) was present in 41% of subjects, but only 14% had LBW. Preterm, compared with term, delivery was associated with an increased risk of death or transplant at age 6 years (all: hazard ratio = 2.58, confidence interval = 1.43-4.67; Norwood survivors: hazard ratio = 1.96, confidence interval = 1.10-3.49) independent of LBW and weight for gestational age. Preterm delivery, early-term delivery, LBW, and SGA were each associated with lower weight at 6 years. Neurodevelopmental outcomes were worst in the LBW cohort. CONCLUSIONS: Preterm delivery in HLHS was associated with worse survival, even beyond Norwood hospitalization. LBW, SGA, and early-term delivery were associated with worse growth but not survival. LBW was associated with worse neurodevelopment, despite similar length of stay and complications. These data suggest that preterm birth and LBW (although often concomitant) are not equivalent, impacting clinical outcomes through mechanisms independent of perioperative course complexity.

Impact of Initial Shunt Type on Echocardiographic Indices in Children After Single Right Ventricle Palliations.

Background Heart size and function in children with single right ventricle (RV) anomalies may be influenced by shunt type at the Norwood procedure. We sought to identify shunt-related differences during early childhood after staged surgical palliations using echocardiography. Methods We compared echocardiographic indices of RV, neoaortic, and tricuspid valve size and function at 14 months, pre-Fontan, and 6 years in 241 subjects randomized to a Norwood procedure using either the modified Blalock-Taussig shunt or RV-to-pulmonary-artery shunt. Results At 6 years, the shunt groups did not differ significantly in any measure except for increased indexed neoaortic area in the modified Blalock-Taussig shunt. RV ejection fraction improved between pre-Fontan and 6 years in the RV-to-pulmonary artery shunt group but was stable in the modified Blalock-Taussig shunt group. For the entire cohort, RV diastolic and systolic size and functional indices were improved at 6 years compared with earlier measurements, and indexed tricuspid and neoaortic annular area decreased from 14 months to 6 years. The prevalence of ≥moderate tricuspid and neoaortic regurgitation was uncommon and did not vary by group or time period. Diminished RV ejection fraction at the 14-month study was predictive of late death/transplant; the hazard of late death/transplant when RV ejection fraction was <40% was tripled (hazard ratio, 3.18; 95% CI, 1.41-7.17). Conclusions By 6 years after staged palliation, shunt type has not impacted RV size and function, and RV and valvar size and function show beneficial remodeling. Poor RV systolic function at 14 months predicts worse late survival independent of the initial shunt type. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00115934.

Heart failure after the Norwood procedure: An analysis of the Single Ventricle Reconstruction Trial.

BACKGROUND: Heart failure results in significant morbidity and mortality in young children with hypoplastic left heart syndrome (HLHS) after the Norwood procedure. METHODS: We studied subjects enrolled in the prospective Single Ventricle Reconstruction (SVR) Trial who survived to hospital discharge after a Norwood operation and were followed up to age 6 years. The primary outcome was heart failure, defined as heart transplant listing after Norwood hospitalization, death attributable to heart failure, or symptomatic heart failure (New York Heart Association [NYHA] Class IV). Multivariate modeling was undertaken using Cox regression methodology to determine variables associated with heart failure. RESULTS: Of the 461 subjects discharged home following a Norwood procedure, 66 (14.3%) met the criteria for heart failure. Among these, 15 died from heart failure, 39 were listed for transplant (22 had a transplant, 12 died after listing, and 5 were alive and not yet transplanted), and 12 had NYHA Class IV heart failure but were never listed. The median age at heart failure identification was 1.28 (interquartile range 0.30 to 4.69) years. Factors associated with early heart failure included post-Norwood lower fractional area change, need for extracorporeal membrane oxygenation, non-Hispanic ethnicity, Norwood perfusion type, and total support time (p < 0.05). CONCLUSIONS: By 6 years of age, heart failure developed in nearly 15% of children after the Norwood procedure. Although transplant listing was common, many patients died from heart failure before receiving a transplant or without being listed. Shunt type did not impact the risk of developing heart failure.