OBJECTIVE To elucidate the multi-omics molecular characteristics of heart failure with preserved ejection fraction (HFpEF) patients with qi deficiency and blood stasis syndrome, providing a scientific foundation for individualized traditional Chinese medicine (TCM) interventions.

METHODS Between July 2022 and June 2023, 27 HFpEF patients with qi deficiency and blood stasis syndrome and 22 disease controls were enrolled. Metabolomics analysis was performed on peripheral blood plasma samples from all subjects using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to screen for differentially expressed metabolic substances between groups. Transcriptomic sequencing (Bulk RNA-seq) and tandem mass tag (TMT) labeling quantitative proteomic analysis were employed to analyze peripheral blood leukocyte samples from 7 patients with HFpEF of qi deficiency and blood stasis syndrome and 7 disease controls, identifying differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) between the two groups, followed by bioinformatics analysis.

RESULTS Metabolomics results showed that 222 DEGs were screened and 36 were identified between the HFpEF qi deficiency and blood stasis syndrome group and the disease control group. These DEGs were mainly enriched in glycine/serine threonine metabolism, the tricarboxylic acid cycle, and pyruvate metabolism pathways, suggesting that HFpEF patients have amino acid and fatty acid metabolism disorders and impaired energy metabolism. Transcriptomic analysis identified 6 433 DEGs, enriched in biological processes such as inflammatory response, oxidative stress, autophagy, phosphorylation, calcium signaling pathway, and cardiac function. Proteomic analysis revealed 1 124 DEPs, associated with neutrophil extracellular trap formation, the HIF-1 signaling pathway, and metabolic pathways. Multi-omics integration analysis showed that Ca²⁺/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) and the HIF-1 signaling pathway are key molecular hubs.

CONCLUSION HFpEF patients with qi deficiency and blood stasis syndrome exhibit distinct multi-omics alterations characterized by hypoxia, inflammation, autophagy, and metabolic dysfunction. Dysregulation of the HIF-1 signaling pathway and upregulation of CaMKII may be potential therapeutic targets.