Mortality in acute myocardial infarction complicated by cardiogenic shock (AMI-CS) remains high. The complex interplay of innate and acquired immune cell activation with haemodynamic compromise during the acute phase of myocardial ischaemia is incompletely understood. This study characterises the dynamic immune response in patients with AMI-CS with the aim of identifying a clinically useful biomarker.
We applied unbiased single-cell RNA sequencing to peripheral blood immune cells of patients with AMI-CS over a period from admission to 72 h after coronary revascularisation and to healthy control (Ctrl) subjects profiling over 171 000 cells at a university hospital in Germany. Trajectories of differential gene expression were analysed with a focus on immune activation pathways. Clinical validation was performed in 4 355 patients with AMI and AMI-CS from a prospective, multicentre cohort in Switzerland (SPUM-ACS).
High-resolution scRNA-seq revealed profound monocyte-driven immune activation, with a strong and previously unrecognised induction of the cardiogenic shock marker 1 (CSM1). CSM1 expression in monocytes increased more than eight-fold in AMI-CS patients compared with control individuals (fold-change at 24 h AMI-CS vs. Ctrl: 8.29, P < 0.001) mirroring activation of several key immune response pathways. External validation in the Swiss cohort showed higher circulating CSM1 (cCSM1) levels associated with systemic inflammation, haemodynamic compromise, and poor outcomes. After multivariable-adjustment, high cCSM1 independently predicted 30-day mortality (AMI fully adjusted + GRACE 2.0 per log2 increase HR: 2.22, 95% CI 1.44–3.43, P < 0.001; AMI-CS fully adjusted + IABP-SHOCK II per log2 increase HR: 5.83, 95% CI 1.79–19.01, P = 0.0035) and 1-year mortality (AMI fully adjusted + GRACE 2.0 per log2 increase HR: 1.98, 95% CI 1.44–2.71, P < 0.001; AMI-CS fully adjusted per log2 increase HR: 2.55, 95% CI 1.26–5.19, P = < 0.01). Circulating CSM1 showed favourable discriminatory abilities compared to other inflammatory markers including high-sensitivity C-reactive protein and the neutrophil-lymphocyte-ratio, and improved risk discrimination and reclassification beyond the GRACE score.
Circulating CSM1 is a novel immune response biomarker with incremental prognostic utility for short- and long-term mortality in AMI and AMI-CS. These findings highlight the potential of single-cell immunoprofiling to identify clinically relevant phenotypes that may guide future management strategies in AMI and AMI-CS.
