Intracoronary stem cell transplant in ischemic heart disease: a meta-analysis of randomized trials

OBJECTIVE: Ischemic heart disease is a leading cause of morbidity and mortality. In this study, we assessed the efficacy of intracoronary stem cell transplantation on left ventricular function (LVEF) in acute myocardial infarction, chronic ischemic heart disease, and severe ischemic heart failure.  

MATERIALS AND METHODS: We conducted a meta-analysis of randomized trials from 2002 to 2025. Mean difference in LVEF between treated and control patients at 6-months after infusion was calculated according to analysis of covariance. Heterogeneity among studies was assessed by the Cochrane’s Q, Tau², and I² statistics. The primary outcome was the LVEF difference at follow-up. Secondary outcomes were comparisons among the type and number of transplanted stem cells.

RESULTS: The analysis included 82 randomized controlled trials totaling 5,781 patients (3,048 treated and 2,733 controls) affected by acute myocardial infarction (AMI, n. 70), chronic ischemic heart disease (CIHD, n. 5), and ischemic heart failure (IHF, n. 7). Stem cells were bone marrow, mesenchymal, peripheral blood, and cardiac stem cells in 58, 15, 6 and 3 studies, respectively. Median infused cells were 100 x 10⁶.  LVEF increased 3.3% overall and 8.2%, 5.3% and 2.7% in CIHD, IHF and AMI, respectively. LVEF increased 2% per each 10⁹ cells. CIHD improved from mild (46%) to normal (54%) and IHF from severe (30%) to moderate (38%) functional class. Study heterogeneity decreased over publication year, and there is evidence for publication bias, although the Egger’s test resulted in a non-significant result. Intracoronary stem cells induced a significant decrease in mean New York Heart Association (NYHA) functional class from baseline to 6 and 12 months after transplant (2.6, 1.8, and 1.9, respectively; t-test p = 0.002) in ischemic heart failure patients.  

CONCLUSIONS: Intracoronary stem cell transplantation improves LVEF in acute and chronic ischemic heart disease and is associated with a reduction of functional class severity. The intracoronary route may be taken into consideration in future trials of stem cell therapy for ischemic heart disease due to its relative manageability and simplicity.

Graphical Abstract