Background. Ischemic heart disease (IHD) and dilated cardiomyopathy (DCM) are the two most common etiologies of heart failure (HF). Both forms share common characteristics including ventricle dilation in the final stage. Immune mechanisms in HF are increasingly highlighted and have been implicated in the pathogeneses of IHD and DCM. A better understanding of adhesion molecule expression and correlated immune cell infiltration could enhance disease detection and improve therapeutic targets. Objective. This study was performed to explore the common mechanisms underlying IHD and DCM.Methods. After searching the Gene Expression Omnibus database, we selected the GSE42955 and GS57338 datasets for analysis, which contain 29 and 313 samples, respectively. Results. The screening stage revealed that vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1) play pivotal roles in regulating DEGs. Subsequent analyses revealed that VCAM1 was differentially expressed in the myocardium and involved in regulating immune cell infiltration. We also found that dysregulated VCAM1 expression was associated with a higher risk of HF by constructing a clinical risk-predicting model. Conclusions. Collectively, our results suggest that VCAM-1 could be used as a biomarker or therapy target for HF.