Route of delivery and baseline left ventricular ejection fraction, key factors of bone-marrow-derived cell therapy for ischaemic heart disease.
Brunskill SJ., Hyde CJ., Doree CJ., Watt SM., Martin-Rendon E.
AIMS: Previous evaluation of autologous bone-marrow stem-cell (BMSC) therapy following acute myocardial infarction (AMI) suggests that cell dose and timing of stem-cell administration post-MI are important factors in the efficacy of cellular therapy. This study aimed to assess whether route of delivery and baseline left ventricular ejection fraction (LVEF) of the participants may also affect the outcome of BMSC treatment in patients with AMI and ischaemic heart disease (IHD). METHODS AND RESULTS: Randomized controlled trials of BMSCs as treatment for AMI and IHD were identified by searching MEDLINE, EMBASE, the Cochrane Library, and the Current Controlled Trials Register through to November 2008. Twenty-one trials (25 comparisons) with a total of 1091 participants were eligible. Data were analysed using a random-effects model. Improvement in LVEF in favour of the control was observed when BMSC were administered by intracoronary infusion [-0.19% (95% CI, -0.24 to -0.14; P < 0.00001)] in IHD patients. However, the effect on LVEF was statistically significant and in favour of BMSC when cells were delivered by intra-myocardial injection [5.85% (95% CI, 2.50-9.19; P = 0.0006)]. The significant improvement in LVEF observed in AMI patients was independent from the baseline LVEF of the participants. However, in patients suffering from chronic IHD, increase in LVEF was significant only in the group with lower LVEF at baseline [4.42% (CI, 1.87-6.96; P = 0.0007)]. CONCLUSION: Clinical evidence suggests that route of delivery and baseline LVEF influence the effect of BMSC therapy in treating AMI and chronic IHD.