Safety and Efficacy of Transendocardial Stem Cells Therapy in Chronic Ischemic Heart Failure: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Introduction: Chronic ischemic heart failure is a major global health issue despite advancements in therapy. Stem cell (SC) therapy has emerged as a potential treatment, but its effectiveness remains uncertain. This study aimed to systematically review and meta-analyze the current evidence on SC therapy's efficacy.

Methods: We conducted a comprehensive literature search in PubMed, Embase, and Cochrane databases up to April 2024. We included randomized controlled trials (RCTs) with blinded designs, focusing on patients with heart failure with reduced ejection fraction (HFrEF) treated with mesenchymal stem cells compared to placebo or sham interventions via percutaneous endomyocardial catheter systems. Data extraction, performed independently by two authors, focused on safety and efficacy variables. The meta-analysis used a random-effects model, with sensitivity analyses to address study heterogeneity.

Results: Twenty studies were included in the meta-analysis. Significant improvements were observed in the stem cell group for left ventricular end-systolic volume (LVESV) (pooled effect size -7.59, 95% CI [-12.28 to -2.89], P=0.002) and stress SPECT outcomes (pooled effect size - 5.33, 95% CI [-6.73 to -3.93], P<0.00001). Sensitivity analysis reduced heterogeneity in left ventricular end-diastolic function (LVEDF) (P=0.01, I²=54%) and revealed a significant benefit for stem cell therapy (pooled effect size -3.87, 95% CI [-6.77 to -0.97], P=0.009). No significant effects were observed for left ventricular ejection fraction (LVEF) or myocardial oxygen consumption (MVO2). Functional improvements in New York Heart Association (NYHA) classification were noted (OR=4.22, 95% CI [1.14-15.68], P=0.03), though no significant differences were found in safety outcomes, including major cardiovascular events, mortality, or rehospitalization rates.

Conclusion: Transendocardial SC therapy shows promise in improving certain cardiac parameters, though its impact on LVEF and MVO2 remains inconclusive, indicating the need for further research.