Gene-set and proteomic signatures associated with survival after in-hospital cardiac arrest

Background
In‑hospital cardiac arrest (IHCA) is associated with high mortality despite advances in resuscitation and post–cardiac arrest care. While individual inflammatory and neurologic biomarkers have been studied, less is known about coordinated proteomic and pathway‑level responses associated with survival after IHCA.
Methods
In this prospective observational study, adult patients resuscitated after IHCA were enrolled at a tertiary academic medical center. Plasma samples were obtained at baseline (T0), 6 hours (T6), and 24 hours (T24) following return of spontaneous circulation (ROSC), when clinically feasible. High‑dimensional proteomic profiling was performed using the Olink® Explore 1536 platform. Survival‑associated proteins were identified using linear mixed‑effects models, and gene set enrichment analysis (GSEA) was performed to identify biologically coherent pathways.
Results
Ninety‑five patients were enrolled. Due to early mortality and clinical constraints, analyzable samples were obtained from overlapping patient subsets at T0 (n=24), T6 (n=21), and T24 (n=49). Individual protein‑level differences were limited at baseline. The greatest divergence between survivors and non‑survivors occurred at 6 hours, characterized by enrichment of immune‑metabolic, mitochondrial, and transcriptional pathways. At 24 hours, pathway enrichment narrowed toward chemokine signaling, GPCR‑mediated responses, and oxidative stress. Baseline pathway signals were nominal and did not meet false discovery rate thresholds.
Conclusions
Survival following IHCA is associated with dynamic, time‑dependent proteomic and pathway‑level signatures, with the most pronounced biological divergence occurring early after resuscitation. These findings support the concept of time‑sensitive molecular phenotyping in post–cardiac arrest care and provide a foundation for future translational studies.