Cardiomyocyte regeneration therapy and its effect on LVEF and scar size- a systematic review and meta-analysis

Abstract

Background: Myocardial infarction (MI) results in loss of cardiomyocytes leading to heart failure. Despite advancements in pharmacotherapy and interventions such as revascularization, ischemic heart failure remains a challenge. Recent advancements in stem cell therapies, genetic engineering and bioengineering have shown to improve cardiac function and quality of life. Methodology: Following PRISMA guidelines, randomized controlled trials clinical trials from last 12 years were systematically reviewed. All the patients included in these studies had ischemic heart failure and were subjected to different types of stem cell therapies. Protocol for this meta-analysis is registered on PROSPERO (Registration no: CRD42023399263). Data extraction and Quality assessment was done according to Cochrane handbook of systematic reviews and meta-analysis. Meta-analysis was conducted using Revman, and a random-effect model was used to calculate weighted mean differences (WMD) in left ventricular ejection fraction (LVEF), scar size and Minnesota Living with Heart Failure score (MLHFQ) pre- and post-intervention. Results: The pooled mean difference (MD) for scar size reduction at 6 months follow-up was − 0.36; (95%CI [-0.63, -0.10]), I2 = 71% (p < 0.0001) and at 12 months follow-up was − 0.62; (95%CI [-1.03, -0.21]), I2 = 78% (p < 0.0001) with a positive effect direction. Weight of the studies ranged from 5.4 to 10.8% and 9.6–14.1% at 6 months and 12 months follow-up respectively. The pooled data analysis at 6 months and 12 months follow-up revealed weighted mean difference 0.44; (95% CI [0.13–0.75]), I2 = 85% (p < 0.00001) and 0.64; 95% CI [0.14–1.14], I2 = 85% (p < 0.00001) respectively. For MHLFQ score pooled weighted mean difference was calculated for 286 patients which revealed mean difference − 0.38, (95% CI [-0.71-0.05]) (p = 0.02), I2 = 69% (p < 0.002). Sensitivity analysis by excluding ‘Gujjaro et al. 2016’ revealed weighted mean difference − 0.49; (95% CI [-0.74-0.25]) (p < 0.0001), I2 = 72% (p = 0.09). Conclusions: Our meta-analysis not only demonstrated consistent improvements in LVEF and reductions in scar size but also improvement in quality of life with stem cell therapies, however, the heterogeneity among studies calls for a need of standardized protocols and further research in optimizing these therapies to improve cardiomyocyte regeneration and overall cardiac repair.