Abstract: Objective To investigate the associations of galectin-4 （Gal-4） and histone deacetylase 6 （HDAC6） with cardiac functional class and Meta-Analysis Global Group in Chronic Heart Failure （MAGGIC） score in patients with chronic heart failure （CHF） and to evaluate their prognostic value. Methods This retrospective study included 218 patients with CHF hospitalized at Xinxiang Central Hospital from June 2018 to June 2021. Prognosis was assessed based on the occurrence of major adverse cardiovascular events （MACE） over a 3-year period, and patients were divided into a MACE group （n=74） and a non-MACE group （n=144）. Serum levels of Gal-4 and HDAC6 were measured via enzyme-linked immunosorbent assay （ELISA）. Pearson and Spearman's correlation analysis was used to assess the correlations of serum Gal-4 and HDAC6 levels with cardiac function, MAGGIC score, and prognosis in patients with CHF. Multivariate Cox regression and Kaplan-Meier analysis were used to evaluate prognosis. Receiver operating characteristic （ROC） curve analysis was used to evaluate the predictive value of each biomarker for the occurrence of MACE within 3 years in patients with CHF. Results Serum Gal-4 and HDAC6 levels in patients with CHF increased significantly as NYHA class increased （both P<0.01）. In patients with CHF, Gal-4 was weakly to moderately positively correlated with the MAGGIC score （r=0.428）, BUN （r=0.247）, and Scr （r=0.178）. HDAC6 was also weakly to moderately positively correlated with the MAGGIC score （r=0.416）, UA （r=0.284）, and NT-proBNP （r=0.191） （all P<0.05）. Serum Gal-4 and HDAC6 levels were significantly higher in the MACE group than in the non-MACE group （both P<0.01）. High serum levels of Gal-4 （HR=1.524, 95%CI：1.238-1.876） and HDAC6 （HR=1.037, 95%CI：1.006-1.070） were independent risk factors for MACE within 3 years in patients with CHF （both P<0.05）. The cumulative incidence of MACE over 3 years was significantly higher in the group with high expression of both Gal-4 and HDAC6 compared with both the group with low expression of both markers and the group with high expression of one marker and low expression of the other （all P<0.01）. The combined Gal-4 and HDAC6 model （Gal-4+HDAC6, AUC=0.824） and the MAGGIC score （AUC=0.840） both exhibited predictive performance for MACE within 3 years in patients with CHF,and there was no significant difference between them （Z=0.488, P=0.626）. Conclusion Serum Gal-4 and HDAC6 may serve as potential biomarkers reflecting disease severity and long-term risk of MACE in patients with CHF. Combined measurement of Gal-4 and HDAC6 provides a novel and effective tool for risk stratification and prognostic assessment in this population.

Key words: Gal-4, HDAC6, chronic heart failure, major adverse cardiovascular events, independent risk factors, predictive value