Significant causal relationship factors: C-X-C motif chemokine 9 (CXCL9, OR = 1.140, 95% CI = 1.052–1.234, P = 0.001, PFDR = 0.005); Interferon-gamma (IFN-γ, OR = 1.140, 95% CI = 1.049–1.240, P = 0.002, PFDR = 0.0363); Leukemia Inhibitory Factor Receptor (LIFR, OR = 0.892, 95% CI = 0.833–0.956, P = 0.001, PFDR = 0.0004); Urokinase-type Plasminogen Activator (UPA, OR = 0.907, 95% CI = 0.863–0.953, P = 0.0001, PFDR = 0.005); In these, CXCL9 and IFN-γ are identified as risk factors promoting heart failure, whereas LIFR and UPA are protective factors against heart failure. This evidence concerns the gene CXCL9 and heart failure.