Background. The inflammatory response is important in dilated cardiomyopathy (DCM). However, the expression of inflammatory response genes (IRGs) and regulatory mechanisms in DCM has not been well characterized. Methods. We analyzed 27,665 cells of single-cell RNA sequencing dataset of four DCM samples and two healthy controls (HC). IRGs among differentially expressed genes (DEGs) of active cell clusters were screened from the Molecular Signatures Database (MSigDB). The bulk sequencing dataset of 166 DCM patients and 166 HC was analyzed to explore the common IRGs. The biological functions of the IRGs were analyzed according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. IRG-related transcription factors (TFs) were determined using the TRRUST database. The protein–protein interaction (PPI) network was constructed using the STRING database. Then, we established the noncoding RNA (ncRNA) regulatory network based on the StarBase database. Finally, the potential drugs that target IRGs were explored using the Drug Gene Interaction Database (DGIdb). Results. The proportions of dendritic cells (DCs), B cells, NK cells, and T cells were increased in DCM patients, whereas monocytes were decreased. DCs expressed more IRGs in DCM. The GO and KEGG analyses indicated that the functional characteristics of active cells mainly focused on the immune response. Thirty-nine IRGs were commonly expressed among active cell cluster DEGs, bulk RNA DEGs, and inflammatory response-related genes. ETS1 plays an important role in regulation of IRG expression. The competing endogenous RNA regulatory network showed the relationship between ncRNA and IRGs. Sankey diagram showed that arachidonate 5-lipoxygenase (ALOX5) played a major role in regulation between TFs and potential drugs. Conclusion. DCs infiltrate into the myocardium and contribute to the immune response in DCM. The transcription factor ETS1 plays an important role in regulation of IRGs. Moreover, ALOX5 may be a potential therapeutic target for DCM.
Background Congestive heart failure (HF) is a common condition in the intensive care unit (ICU). Cardiomyopathy is an important etiological factor in HF. However, few studies have explored the effect of cardiomyopathy on the prognosis of HF. This study explored the association between comorbid cardiomyopathy and the outcomes of critically ill patients with congestive HF. Methods A retrospective cohort study was performed using data extracted from Medical Information Mart for Intensive Care IV (MIMIC-IV) database. All adult patients with the first ICU admission were enrolled as participants but those diagnosed with cardiomyopathy alone were excluded. The demographics, comorbidities, vital signs, laboratory tests, scoring systems, and treatments of patients were extracted to further analyze. The composite endpoints included in-hospital mortality, cardiac arrest, and re-admission to the ICU. The association between cardiomyopathy comorbidity and the composite endpoints was assessed using propensity-score matching (PSM) and multivariable logistic regression models. Results A total of 27,901 critically ill patients were enrolled, including 1,023 patients diagnosed with cardiomyopathy and congestive HF. The average age of the cohort was 64.37±17.36 years, and 58.13% of the patients were men. The ethnicity of patients was mainly white (64.67%). Multivariable logistic regression analyses found the risk of composite endpoints in patients with cardiomyopathy was higher than other groups [odds ratio (OR) =1.87; 95% confidence interval (CI): 1.62–2.15; P<0.001]. Compared to patients with congestive HF alone (OR =1.43; 95% CI: 1.26–1.62; P<0.001), patients with cardiomyopathy had a similar risk of in-hospital death (OR =1.35; 95% CI: 1.06–1.71; P=0.014). Moreover, the risks of cardiac arrest (OR =1.53; 95% CI: 1.01–2.34; P=0.029) and re-admission to the ICU (OR =1.74; 95% CI: 1.39–2.17; P<0.001) were both higher in patients with cardiomyopathy than other groups. After PSM, the risk of composite endpoints was still higher in patients with cardiomyopathy (OR =1.64; 95% CI: 1.33–2.02; P<0.001). The association was consistent among patients admitted to the coronary care unit (CCU) and medical ICU (MICU)/surgical ICU (SICU). Conclusions Comorbid cardiomyopathy increased the risk of composite endpoints in patients with congestive HF admitted to the ICU. Cardiomyopathy is related to the poor outcomes of critically ill patients with congestive HF.
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