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Review
. 2014 Apr;35(15):989-98.
doi: 10.1093/eurheartj/eht372. Epub 2013 Sep 11.

Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction: a collaborative meta-analysis

Affiliations
Review

Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction: a collaborative meta-analysis

Ronak Delewi et al. Eur Heart J. 2014 Apr.

Abstract

Aims: The objective of the present analysis was to systematically examine the effect of intracoronary bone marrow cell (BMC) therapy on left ventricular (LV) function after ST-segment elevation myocardial infarction in various subgroups of patients by performing a collaborative meta-analysis of randomized controlled trials.

Methods and results: We identified all randomized controlled trials comparing intracoronary BMC infusion as treatment for ST-segment elevation myocardial infarction. We contacted the principal investigator for each participating trial to provide summary data with regard to different pre-specified subgroups [age, diabetes mellitus, time from symptoms to percutaneous coronary intervention, infarct-related artery, LV end-diastolic volume index (EDVI), LV ejection fraction (EF), infarct size, presence of microvascular obstruction, timing of cell infusion, and injected cell number] and three different endpoints [change in LVEF, LVEDVI, and LV end-systolic volume index (ESVI)]. Data from 16 studies were combined including 1641 patients (984 cell therapy, 657 controls). The absolute improvement in LVEF was greater among BMC-treated patients compared with controls: [2.55% increase, 95% confidence interval (CI) 1.83-3.26, P < 0.001]. Cell therapy significantly reduced LVEDVI and LVESVI (-3.17 mL/m², 95% CI: -4.86 to -1.47, P < 0.001; -2.60 mL/m², 95% CI -3.84 to -1.35, P < 0.001, respectively). Treatment benefit in terms of LVEF improvement was more pronounced in younger patients (age <55, 3.38%, 95% CI: 2.36-4.39) compared with older patients (age ≥ 55 years, 1.77%, 95% CI: 0.80-2.74, P = 0.03). This heterogeneity in treatment effect was also observed with respect to the reduction in LVEDVI and LVESVI. Moreover, patients with baseline LVEF <40% derived more benefit from intracoronary BMC therapy. LVEF improvement was 5.30%, 95% CI: 4.27-6.33 in patients with LVEF <40% compared with 1.45%, 95% CI: 0.60 to 2.31 in LVEF ≥ 40%, P < 0.001. No clear interaction was observed between other subgroups and outcomes.

Conclusion: Intracoronary BMC infusion is associated with improvement of LV function and remodelling in patients after ST-segment elevation myocardial infarction. Younger patients and patients with a more severely depressed LVEF at baseline derived most benefit from this adjunctive therapy.

Keywords: Bone marrow cells; Meta-analysis; ST-segment elevation myocardial infarction; Ventricular function.

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Figures

Figure 1
Figure 1
Flow diagram of studies included in this meta-analysis. RCTs, randomized controlled trials. See Supplementary material online, Appendix S2 for a list of identified studies.
Figure 2
Figure 2
Pooled improvement of left ventricular ejection fraction (LVEF) of included cell therapy trials assessing different subgroups. CI, confidence interval; IRA, infarct-related artery; LAD, left anterior descending artery; LCX, left circumflex artery; LVEDVI, left ventricular end-diastolic volume index; LVEF, left ventricular ejection fraction; MVO, microvascular obstruction; PCI, percutaneous coronary intervention; RCA, right coronary artery. ¥ frequencies can vary across subgroups due to missing baseline characteristics values. *P-value for subgroup differences.
Figure 3
Figure 3
Pooled improvement of left ventricular end-diastolic volume index (LVEDVI) of included cell therapy trials assessing different subgroups. CI, confidence interval; IRA, infarct related artery; LAD, left anterior descending artery; LCX, left circumflex artery; LVEDVI, left ventricular end-diastolic volume index; LVEF, left ventricular ejection fraction; MVO, microvascular obstruction; PCI, percutaneous coronary intervention; RCA, right coronary artery. ¥ frequencies can vary across subgroups due to missing baseline characteristics values. *P-value for subgroup differences.
Figure 4
Figure 4
Pooled improvement of left ventricular end-systolic volume (LVESVI) of included cell therapy trials assessing different subgroups. CI, confidence interval; IRA, infarct-related artery; LAD, left anterior descending artery; LCX, left circumflex artery; LVEDVI, left ventricular end-diastolic volume index; LVESVI, left ventricular end-systolic volume index; LVEF, left ventricular ejection fraction; MVO, microvascular obstruction; PCI, percutaneous coronary intervention; RCA, right coronary artery. ¥ frequencies can vary across subgroups due to missing baseline characteristics values. *P-value for subgroup differences.

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