Objective:To investigate the effect of Xuefu Zhuyu Decoction on myocardial protection and the interaction between Cadherin-NrF2 pathway and ferroptosis in patients with chronic heart failure resulting from qi deficiency and blood stasis. Methods:A case-control study was conducted on 100 patients with heart failure resulting from qi deficiency and blood stasis who received treatment at The First People's Hospital of Huzhou from February 2021 to May 2022. These patients were divided into a basic western medicine group and a Xuefu Zhuyu Decoction group with 50 patients per group using the random number table method. The basic western medicine group received conventional treatment, while the Xuefu Zhuyu Decoction group received treatment with Xuefu Zhuyu Decoction in addition to conventional treatment. Both groups were treated continuously for 8 weeks. Interleukin-13, intercellular adhesion molecule-1, nitric oxide, cystatin C, thromboxane B2, soluble cluster of differentiation 40 ligand, vascular endothelial cadherin were detected before and after treatment, and soluble tyrosine kinase receptor AXL (sAXL), soluble stromal lysin-2, and ferric ion levels were determined. The mRNA expression levels of glutathione peroxidase 4 and NrF2 were detected. Syndrome scores were evaluated. Clinical efficacy was compared between the two groups. Results:After treatment, the levels of interleukin-13 [(7.63 ± 1.85) ng/L], intercellular adhesion molecule-1 [(41.71 ± 6.25) ng/L], and cystatin C [(0.61 ± 0.17) ng/L] in the Xuefu Zhuyu Decoction group were significantly lower than those in the basic western medicine group [(10.56 ± 2.13) ng/L, (50.11 ± 8.34) ng/L, (1.03 ± 0.22) ng/L, t = 7.34, 5.69, 10.68, all P < 0.05]. The levels of soluble cluster of differentiation 40 ligand [(14.61 ± 1.19) μg/L] and thromboxane B2 [(40.18 ± 7.24) ng/L] in the Xuefu Zhuyu Decoction group were significantly lower than those in the basic western medicine group [(16.03 ± 1.47) μg/L, (53.37 ± 10.16) ng/L, t = 5.30, 7.47, both P < 0.05], while the level of nitric oxide [(59.92 ± 6.16) μmol/L] in the Xuefu Zhuyu Decoction group was significantly higher than that in the basic Western medicine group [(53.17 ± 5.49) μmol/L, t = 5.78, P < 0.05]. The level of ferric ion [(0.23 ± 0.08) μg/L] in the Xuefu Zhuyu Decoction group was significantly higher than that in the basic western medicine group [(0.16 ± 0.05) μg/L, t = 5.24, P < 0.05]. The levels of vascular endothelial cadherin [(3.02 ± 0.72) ng/L], NrF2 mRNA [(2.11 ± 0.43)], and glutathione peroxidase 4 mRNA [(4.65 ± 0.74)] in the Xuefu Zhuyu Decoction group were significantly lower than those in the basic western medicine group [(4.34 ± 1.05) ng/L, (2.93 ± 0.56), (5.16 ± 0.88), t = 7.33, 8.21, 3.13, all P < 0.05]. The levels of Galectin-3 [(62.48 ± 6.09) μg/L], soluble stromal lysin-2 [(0.98 ± 0.24) ng/L], and sAXL [(42.16 ± 7.54) ng/L] in the Xuefu Zhuyu Decoction group were significantly lower than those in the basic western medicine group [(70.96 ± 8.15) μg/L, (1.57 ± 0.46) ng/L, (56.11 ± 10.02) ng/L, t = 5.89, 8.04, 7.86, all P < 0.05]. The Xuefu Zhuyu Decoction group had lower scores for shortness of breath or wheezing [(1.06 ± 0.24) points], palpitations [(0.92 ± 0.15) points], fatigue [(0.75 ± 0.17) points], low voice [(0.68 ± 0.16) points], spontaneous sweating [(0.83 ± 0.21) points], fatigue and laziness [(0.73 ± 0.20) points], prone to fatigue [(0.66 ± 0.14) points], and dark complexion or lips [(0.61 ± 0.16) points] compared with the basic western medicine group [(1.65 ± 0.49) points, (1.15 ± 0.27) points, (1.16 ± 0.31) points, (1.12 ± 0.29) points, (1.28 ± 0.32) points, (1.28 ± 0.37) points, (1.01 ± 0.21) points, (0.96 ± 0.25) points, t = 7.64, 5.26, 8.20, 9.39, 8.31, 9.24, 9.80, 8.33, all P < 0.05]. The total response rate of the Xuefu Zhuyu Decoction group was significantly higher than that of the basic western medicine group [(96.00% (48/50) vs. 88.00% (44/50), Z = 1.91, P < 0.05). Conclusion:Treating patients with heart failure with Xuefu Zhuyu Decoction can inhibit inflammation, improve vascular endothelial cell function, regulate Cadherin-NrF2 pathways, reduce oxidative stress injury, further inhibit ferroptosis, reduce the levels of Galectin-3, soluble stromal lysin-2, and sAXL, protect myocardium, relieve clinical symptoms, and improve its efficacy.