Molecular Signatures Underlying Progression from Stage C to Stage D in Non-Ischemic Cardiogenic Shock

Document Type

Conference Proceeding

Publication Date

4-2026

Publication Title

Journal of Heart and Lung Transplantation

Abstract

Purpose: Cardiogenic shock (CS) is a progressive condition in which impaired cardiac function leads to multiorgan dysfunction and high mortality. The molecular mechanisms underlying CS progression remain poorly defined. Transcriptomic profiling of peripheral blood can provide insight into disease mechanisms and potential therapeutic targets. We aimed to characterize transcriptional differences between Stage C and Stage D non-ischemic CS patients

Methods: Peripheral blood samples were collected from Stage C (n = 31) and Stage D (n = 9) non-ischemic CS patients within 24 hours of diagnosis. Bulk RNA sequencing was performed to generate gene expression profiles. Differentially expressed genes (DEGs) were identified by comparing Stage D with Stage C samples. Gene set enrichment analysis was conducted to identify biological pathways. Potential therapeutic compounds were inferred using the Reversal of Gene Expression Score (RGES) framework. Immune cell composition across stages was estimated using the CIBERSORTx. Survivors/non-survivors were compared.

Results: Differential expression analysis identified 87 DEGs (67 upregulated and 20 downregulated) in Stage D vs Stage C. Upregulated genes included MTND2P28, OSBPL1A, PEX11G, SEC14L5, and KCNMA1, while downregulated genes included TRGV10, ACOT11, and NDFIP2. Pathway analysis revealed activation of coagulation, platelet activation, and hemostasis pathways, alongside suppression of adaptive and T cell mediated immune responses, ribosome biogenesis, and rRNA processing. RGES analysis identified several candidate compounds, such as the JAK inhibitor upadacitinib and NSAIDs including ibuprofen and fenofibrate as potential therapies for Stage D. Cellular deconvolution revealed reductions in CD8 T cells, NK cells, CD4 memory cells, mast cells, and monocytes. Additionally, naïve B cells and M0 macrophages were reduced in deceased patients compared to survivors in Stage C group.

Conclusion: Transcriptomic profiling revealed distinct molecular signatures distinguishing Stage D from Stage C non-ischemic CS, characterized by activation of pro-thrombotic and oxidative stress pathways and suppression of adaptive immunity. Reduced immune cell abundance further suggests significant immune dysregulation in Stage D patients, providing insights into potential biomarkers and therapeutic targets for advanced CS.

Volume

45

Issue

5 Suppl

First Page

215

Comments

Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation (ISHLT), Apr 22-26, 2026, Toronto, Canada

Last Page

216

DOI

10.1016/j.healun.2026.02.460

ISSN

1053-2498

Link to Full Text

Share

COinS