Abstract

Introduction: Results from randomized controlled trials (RCTs) of bone marrow cell (BMC) therapy for cardiac repair have been discordant. The true impact of BMC therapy in patients with chronic ischemic heart disease (CIHD) and ischemic heart failure remain unclear. Hypothesis: We hypothesized that BMC injection would improve clinical outcomes and left ventricular (LV) parameters in patients with CIHD. Methods: We performed a systematic review and meta-analysis of data from RCTs of BMC therapy on LV ejection fraction (LVEF), LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), infarct scar size, and clinical outcomes in patients with CIHD. Database searches based on specified criteria identified 15 eligible RCTs (enrolling 648 CIHD patients). Changes in predefined parameters were analyzed with random-effects meta-analysis. Peto odds ratio (OR) was calculated for clinical outcomes. Results: Compared with standard therapy, BMC transplantation improved LVEF (3.84%; 95% confidence interval [CI], 2.30 to 5.38; P<0.00001), reduced scar size (-5.90%; 95% CI, -8.03 to -3.78; P<0.00001) and LVESV (-10.37 ml; 95% CI, (-18.56 to -2.18; P=0.01). Reduction in LVEDV (-1.84 ml; 95% CI, -9.13 to 5.46; P=0.62) was not significant. The improvement in LVEF in BMC-treated patients was also significant (1.78%; 95% CI: 0.63 to 2.93; P=0.002) in a separate analysis of RCTs that used MRI. Importantly, BMC therapy reduced all-cause mortality (OR: 0.35; 95% CI 0.16 to 0.73; P=0.005) and incidence of cerebrovascular accident (CVA) (OR: 0.07; 95% CI, 0.01 to 0.55; P=0.01) and tended to reduce the incidence of heart failure (OR: 0.36; 95% CI 0.11 to 1.14; P=0.08) in patients with CIHD (Table). Conclusions: BMC therapy improves LVEF, LVESV, and infarct scar size in patients with CIHD. The improvement in LVEF was also confirmed in meta-analysis of RCTs using MRI. Importantly, these numerically small benefits translated into improved clinical outcomes in BMC-treated CIHD patients.

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