Peripheral blood transcriptomes and a single-cell atlas suggest a monocyte-associated immune recovery-failure axis in STEMI

Background: Patients with ST-segment elevation myocardial infarction (STEMI) continue to show substantial inflammatory heterogeneity after reperfusion therapy, and recovery trajectories may differ markedly across patients. Compared with traditional diagnostic models, characterizing the dynamic immune trajectory from acute inflammation toward recovery may better identify programs associated with impaired resolution. This study aimed to construct an immune recovery-failure framework that is transferable across cohorts and anchored by single-cell data. Methods: We integrated six public GEO peripheral-blood bulk transcriptome cohorts and one public single-cell RNA-seq dataset. An acute-to-recovery immune axis was constructed from directionally concordant longitudinal and cross-sectional contrasts, and a recovery-failure phenotype was defined in the discovery longitudinal cohort from paired transcriptomic features. An 18-gene monocyte-associated module was then derived using bulk recovery-failure associations, monocyte specificity, monocyte-state differences, and pseudotime information. External cohorts were used to evaluate temporal transfer and baseline-to-follow-up associations rather than definitive clinical prediction, and the single-cell dataset was used for donor-aware cell-type anchoring and exploratory state-level interpretation. Results: Among 81 STEMI patients who met the longitudinal definition criteria, unsupervised stratification classified 35 as recovery-failure patients and 46 as recovery-sufficient patients. We constructed an 18-gene monocyte-associated recovery-failure module. The module distinguished the two transcriptomically defined groups in the discovery cohort and declined from the acute phase toward recovery in external longitudinal cohorts. Baseline module burden was associated with later composition-adjusted inflammatory burden, but this was interpreted as a baseline-to-follow-up association rather than clinical event prediction. At the single-cell level, donor-aggregated lesion-associated shifts were largest in monocytes, and the module decreased along the acute-high-to-recovery-biased monocyte pseudotime direction. In 1,000 matched random monocyte-gene modules, the observed module showed a higher aggregate recovery statistic than nearly all random signatures. Conclusions: We propose a STEMI immune recovery-failure framework derived from public peripheral-blood transcriptomes, evaluated across independent longitudinal datasets, and linked to monocyte state variation in a public single-cell context. The framework is does not evidence of a causal mechanism or a validated hard-endpoint prediction model; rather, it provides a reproducible transcriptomic description of impaired inflammatory resolution that should be tested prospectively and experimentally.