Immune Cell-Mediated Inflammation in Heart Failure: Subset Heterogeneity and Targeted Therapy.

Heart failure (HF) is the end-stage manifestation of various cardiovascular diseases, affecting over 64 million patients globally. Current standard therapies have substantially improved the prognosis of patients with HF with reduced ejection fraction (HFrEF), but show limited efficacy in HF with preserved ejection fraction (HFpEF), and the overall cure rate remains unsatisfactory. Persistent low-grade sterile inflammation mediated by immune cells is a core pathological driver of HF onset and progression. The high complexity of the cardiac immune microenvironment, along with the phenotypic and functional heterogeneity of immune cells, has made targeted immunotherapy a key research focus in this field. This review focuses on the core perspective of immune cell subpopulation heterogeneity, systematically summarizing the functional characteristics, cell interaction networks, and targeted treatment progress of key immune cells in HF. The aim is to provide comprehensive academic references for basic research and clinical translation in this field. Based on relevant literature published in PubMed from 2021 to 2026, this review systematically summarizes the heterogeneity characteristics and functional transition patterns of macrophages, T cells, neutrophils, and dendritic cells in HF. It dissects the local interaction network between immune cells and resident cardiac cells (including cardiomyocytes and fibroblasts), as well as the cross-organ regulatory mechanism of the immune-adipose-heart axis. Meanwhile, the latest research progress in small-molecule drugs, biological agents, and novel therapeutic strategies targeting immune cells is comprehensively summarized. Finally, this review identifies gaps in current research regarding the spatiotemporal dynamic evolution of immune cells, clinical translation, therapeutic precision and safety, and cross-system regulatory mechanisms, and outlines future directions including high-resolution spatiotemporal immune atlas construction, precise targeting technology development, and individualized immune diagnosis and treatment.