Plasma multi-omics identify early pathogenesis and biomarkers of SCD post-AMI

Early identification and treatment of Sudden Cardiac Death (SCD) post-myocardial infarction (MI) are currently limited by unclear warning indicators and elusive pathogenesis. Here, we constructed a comprehensive multi-omics blood atlas in the acute phase of AMI from 55 pairs of SCD patients and matched survivors, confirmed immune dysregulation and metabolic disorders as the biological hubs leading to post-MI SCD. Targeted proteome quantification identified a TOP4 protein-based biomarker panel, which were validated by internal and external cohorts, and confirmed a superior early prediction power of SCD to traditional clinical risk models. Further interventions targeting complement factor D (CFD) suggested a potential therapeutic strategy for high-risk MI. Our study provided valuable knowledge about the molecular changes and pathogenesis of SCD, shed light on accurate risk stratification and potential therapeutic targets in high SCD-risk MI. Overall design: After informed consent was obtained, fasting blood samples (5 mL) were collected within 24 hours after emergent admission using EDTA tubes.We collected 110 samples (55 SCD and their matched survivor).Total RNA from peripheral blood mononuclear cells (PBMCs) which were separated within 20 min after blood collection was isolated using TRIzol™ reagent (Invitrogen, Carlsbad, CA, USA), followed by 15 min incubation at room temperature and subsequent freezing at -80°C before total RNA extraction.