BackgroundMyocardial infarction (MI) is a common cardiac condition with a high incidence of morbidity and mortality. Despite extensive medical treatment for MI, the development and outcomes of post-MI heart failure (HF) continue to be major factors contributing to poor post-MI prognosis. Currently, there are few predictors of post-MI heart failure.MethodsIn this study, we re-examined single-cell RNA sequencing and bulk RNA sequencing datasets derived from the peripheral blood samples of patients with myocardial infarction, including patients who developed heart failure and those who did not develop heart failure after myocardial infarction. Using marker genes of the relevant cell subtypes, a signature was generated and validated using relevant bulk datasets and human blood samples.ResultsWe identified a subtype of immune-activated B cells that distinguished post-MI HF patients from non-HF patients. Polymerase chain reaction was used to confirm these findings in independent cohorts. By combining the specific marker genes of B cell subtypes, we developed a prediction model of 13 markers that can predict the risk of HF in patients after myocardial infarction, providing new ideas and tools for clinical diagnosis and treatment.ConclusionSub-cluster B cells may play a significant role in post-MI HF. We found that theSTING1, HSPB1, CCL5, ACTN1, andITGB2genes in patients with post-MI HF showed the same trend of increase as those without post-MI HF.