AbstractThe mortality of heart failure after acute myocardial infarction (AMI) remains high. The aim of the present study was to analyze hub genes and immune infiltration in patients with AMI and heart failure (HF). The study utilized five publicly available gene expression datasets from peripheral blood in patients with AMI who either developed or did not develop HF. The unbiased patterns of 24 immune cell were estimated by xCell algorithm. Single-cell RNA sequencing data were used to examine the immune cell infiltration in heart failure patients. Hub genes were validated by quantitative reverse transcription-PCR (RT-qPCR). In comparison with the coronary heart disease (CHD) group, immune infiltration analysis of AMI patients showed that macrophages M1, macrophages, monocytes, natural killer (NK) cells, and NKT cells were the five most highly activated cell types. Five common immune-related genes (S100A12, AQP9, CSF3R, S100A9, and CD14) were identified as hub genes associated with AMI. Using RT-qPCR, we confirmed FOS, DUSP1, CXCL8, and NFKBIA as the potential biomarkers to identify AMI patients at risk of HF. The study identified several transcripts that differentiate between AMI and CHD, and between HF and non-HF patients. These findings could improve our understanding of the immune response in AMI and HF, and allow for early identification of AMI patients at risk of HF.