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Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease.

ABSTRACT: The study examines the whole blood transcriptome profile before and after cardiopulmonary bypass (CPB) in neonates with hypoplastic left heart syndrome (HLHS), a severe form of congenital heart disease, that can develop low cardiac output syndrome (LCOS). Whole blood mRNA transcriptome profiles of 13 neonates with HLHS before and after their first palliative surgery were analyzed to determine differentially expressed genes and pathways. The median age and weight at surgery were 4 days and 3.2 kg, respectively. Of the 13 patients, 8 developed LCOS. There was no significant difference between CPB, aortic cross clamp, deep hypothermic cardiac arrest times between patients that develop LCOS and those that do not. Upon comparing differential gene expression profiles between patients that develop LCOS and those that do not in pre-operative samples, 1 gene was up-regulated and 13 were down regulated. In the post-operative samples, 4 genes were up-regulated, and 4 genes were down regulated when patients that develop LCOS were compared to those that do not. When comparing post-operative samples to pre-operative samples in the patients that do not develop LCOS, 1484 genes were up-regulated, and 1388 genes were down regulated; while patients that developed LCOS had 2423 up-regulated genes, and 2414 down regulated genes for the same pre to post-operative comparison. Pathway analysis revealed differential regulation of inflammatory pathways (IL signaling, PDGF, NOTCH1, NGF, GPCR) and metabolic pathways (heme metabolism, oxidative phosphorylation, protein metabolism including amino acid and derivatives, fatty acid metabolism, TCA cycle and respiratory electron transport chain). By identifying altered transcriptome profiles related to inflammation and metabolism in neonates with HLHS who develop LCOS after CPB, this study opens for exploration novel pathways and potential therapeutic targets to improve outcomes in this high-risk population.

SUBMITTER: Jain PN

PROVIDER: S-EPMC7925649 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease.

Jain Parag N PN Robertson Matthew M Lasa Javier J JJ Shekerdemian Lara L Guffey Danielle D Zhang Yuhao Y Lingappan Krithika K Checchia Paul P Coarfa Cristian C

Scientific reports 20210302 1

The study examines the whole blood transcriptome profile before and after cardiopulmonary bypass (CPB) in neonates with hypoplastic left heart syndrome (HLHS), a severe form of congenital heart disease, that can develop low cardiac output syndrome (LCOS). Whole blood mRNA transcriptome profiles of 13 neonates with HLHS before and after their first palliative surgery were analyzed to determine differentially expressed genes and pathways. The median age and weight at surgery were 4 days and 3.2 kg ...[more]

PMID: 33654130

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Project description:Vocal fold motion impairment (VFMI) is a known risk factor following congenital heart surgery (CHS). The impact of this diagnosis on utilization and outcomes is unknown.To evaluate the cost, postprocedure length of stay (PPLOS), and outcomes for neonates with VFMI after CHS.A cross-sectional analysis of the 2012 Kids' Inpatient Database (KID) of neonates who underwent CHS was carried out. The KID is an administrative data set of patients, aged 20 years or younger, and contains data on more than 10 million hospitalizations from 44 states. The KID is limited to inpatient hospitalization and contains discharge summary level of data. Patients were limited to those who were born during the hospitalization and those who were aged 28 days or younger at the time of admission for CHS. A weighted total of 4139 neonates who underwent CHS were identified, of which 3725 survived. The proportion of neonates diagnosed with VFMI was 264 (6.92%) of 3725.Congenital heart surgery.Cost of inpatient hospital stay, postprocedure length of stay, odds of pneumonia, gastrostomy tube placement, and tracheostomy tube placement. Risk-adjusted generalized linear models examined differences in cost and PPLOS between neonates who underwent CHS and were diagnosed with VFMI and those who were not. Risk-adjusted logistic regression compared the odds of selected outcomes (gastrostomy, tracheostomy, pneumonia). Models were weighted to provide national estimates.Of 3725 neonates (aged 0-28 days), 2203 (59.1%) were male and 1517 (40.7%) were female. Neonates diagnosed with VFMI had significantly higher total cost by $34 000 (95% CI, 2200-65 000) and PPLOS by 9.1 days (95% CI, 4.6-13.7) compared with those who did not. When PPLOS was included as a covariate in the model for cost, presence of VFMI was no longer significant. There were no differences in odds of pneumonia, gastrostomy, or tracheostomy.Vocal fold motion impairment after CHS was associated with significant increases in cost owing to increased PPLOS. These findings provide a foundation to further investigate standardized screening for VFMI following CHS; early identification and treatment may decrease cost and PPLOS.

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Dataset Information

Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease.

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Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease.

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