Background <p>This study aims to analyze the relations of serum Histone Deacetylase 3 (HDAC3) and Thrombospondin-1 (TSP-1) levels to cardiac function grades, ventricular remodeling, and prognosis of patients with chronic heart failure (CHF).</p> Methods <p>We conducted a retrospective analysis of 128 enrolled CHF patients, with 102 healthy individuals as controls. Baseline data and two-year follow-up records were collected to assess prognosis. Serum levels of HDAC3 and TSP-1 were measured using ELISA, and their correlations with ventricular remodeling indicators such as LVEF, LVEDD, LVFS, BNP, NT-proBNP, and cTnI were analyzed using Pearson’s correlation coefficient.</p> Results <p>No significant differences were observed among participants in terms of age, gender, BMI, comorbidities, smoking history, and drinking history. CHF patients exhibited significantly reduced LVEF and LVFS, while LVEDD, BNP, NT-proBNP, cTnI levels, and serum levels of HDAC3 and TSP-1 were markedly elevated. It was found that serum levels of HDAC3 and TSP-1 increased with worsening cardiac function. Both of them correlated significantly with ventricular remodeling indicators, and their elevation was an independent risk factor for poor prognosis in CHF patients.</p> Conclusion <p>Serum levels of HDAC3 and TSP-1 are elevated in CHF patients, exhibiting significant correlations with ventricular remodeling indicators. Combined detection of these two markers may assist in predicting poor prognosis in CHF patients.</p>