Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of all heart failure (HF) cases, with its prevalence steadily rising due to population aging, obesity, and the prevalence of metabolic diseases. Obesity, a core risk factor for HFpEF, leads to a distinct clinical phenotype and significantly worsens patient prognosis. Given the limitations of body mass index (BMI) in assessing fat distribution, epicardial adipose tissue (EAT)—a metabolically active fat depot closely adjacent to the myocardium—has emerged as a crucial anatomical and functional bridge linking obesity to HFpEF. Compared to BMI, EAT volume demonstrates a stronger predictive value for diastolic dysfunction and adverse clinical outcomes, highlighting its clinical significance. This review outlines the multifaceted mechanisms through which EAT contributes to HFpEF pathogenesis, including mechanical constraint limiting ventricular diastole, lipid infiltration causing myocardial metabolic disorders, pro-inflammatory factor paracrine secretion inducing fibrosis, microvascular dysfunction, arrhythmogenic effects, and protein modification disorders. Targeting EAT has shown promise in reducing its volume, improving inflammatory status, and enhancing cardiac function. As a pathogenic and therapeutic nexus between obesity and HFpEF, further elucidation of EAT-related mechanisms may facilitate precision diagnosis and intervention for this growing population.

Heart failure (HF) has been known as a global health problem, and cardiac remodeling plays an essential role in the development of HF. We hypothesized that YQWY decoction might exert a cardioprotective effect against myocardium inflammation, fibrosis, and apoptosis via activating the interleukin‐10 (IL‐10)/Stat3 signaling pathway. To test this hypothesis, the HF model in rats was established by pressure overload through the minimally invasive transverse aortic constriction (MTAC). Echocardiography was performed to assess the left ventricular function of rats. Myocardial fibrosis in rats was observed by Masson and Picrosirius red staining, and the degree of myocardial apoptosis was detected via TUNEL staining. In addition, expression levels of IL‐10, tumor necrosis factor‐α (TNF‐α), Stat3 (P‐Stat3), P65 (P‐P65), CD68, collagen I, TGF‐β, CTGF, Bax, Bcl‐2, cleaved caspase‐3, and PARP in rat serum and myocardium samples were examined by ELISA, western blot, and immunohistochemistry, respectively. YQWY decoction treatment significantly improved left ventricular function in HF rats, especially in those of the high‐dose group (LVEF%: 51.29 ± 5.876 vs. 66.02 ± 1.264, P < 0.01;, LVFS%: 27.75 ± 3.757 vs. 37.76 ± 1.137, P < 0.01). Furthermore, YQWY decoction markedly inhibited MTAC‐induced myocardial fibrosis as evidenced by downregulated collagen I, TGF‐β, and CTGF in myocardium and alleviated apoptosis (downregulated caspase‐3 and PARP and increased Bcl‐2/Bax ratio in cardiomyocytes). In addition, YQWY decoction decreased the level of the proinflammatory cytokine TNF‐α in both circulating blood and myocardium and attenuated infiltration of inflammatory cells in heart tissue from HF rats. Most importantly, YQWY decoction suppressed MTAC‐induced NF‐κB activation and phosphorylated Stat3 by upregulating IL‐10 in rat heart tissues. Our study showed that YQWY decoction could attenuate MTAC‐induced myocardial inflammation, fibrosis, apoptosis, and reverse the impairment of cardiac function in rats by activating the IL‐10/Stat3 signaling pathway and improving myocardium remodeling. Our findings suggested a therapeutic potential of YQWY decoction in HF.

Background and objectives: Heart failure (HF) is a disease with numerous genetic and environmental factors that affect it. The results of previous studies indicated that immune phenotypes are associated with HF, but there have been inconclusive studies regarding a causal relationship. Therefore, Mendelian randomization (MR) analyses were undertaken to confirm the causal connections between immune phenotypes and HF, providing genetic evidence supporting the association of immune cell factors with HF risk.Methods: We selected instrumental variables that met the criteria based on data from the results of genome-wide association studies (GWAS) of immune phenotype and all-cause HF. An evaluation of the causal association between 731 immune cell factors and HF risk was carried out using the inverse variance weighted (IVW), MR-Egger regression (MR-Egger), and weighted median (WM) analysis methods. To determine the horizontal pleiotropy, heterogeneity, and stability of the genetic variants, the MR-Egger intercept test, Cochran's Q test, MR-PRESSO, and leave-one-out sensitivity analysis were performed.Results: MR principal method (IVW) analysis showed that a total of 38 immune cell-related factors were significantly causally associated with HF. Further analyses combining three methods (IVW, MR-Egger and WME) showed that six exposure factors significantly associated with heart failure, as shown below. The effect of Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell% Dendritic cell, CD39+ CD8+ T cell% CD8+ T cell, CD3 on Central Memory CD4+ T cell on heart failure was positive. Whereas, a reverse effect was observed for CD14+ CD16+ monocyte% monocyte.Conclusion: We investigated the causal relationship between immune phenotypes and all-cause HF. According to the results, Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell% Dendritic cell, CD39+ CD8+ T cell% CD8+ T cell, CD3 on Central Memory CD4+ T cell aggravate HF, and the risk of HF is decreased by CD14+ CD16+ monocyte% monocyte. These phenotypes may serve as new biomarkers, providing new therapeutic insights for the prevention and treatment of all-cause HF.