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, Alexander Hirsch, Jan G. Tijssen, Volker Schächinger, Wojciech Wojakowski, Jérôme Roncalli, Svend Aakhus, Sandra Erbs, Birgit Assmus, Michal Tendera, R. Goekmen Turan, Roberto Corti, Tim Henry, Patricia Lemarchand, Ketil Lunde, Feng Cao, Heikki V. Huikuri, Daniel Sürder, Robert D. Simari, Stefan JanssensKai C. Wollert, Michal Plewka, Stefan Grajek, Jay H. Traverse, Felix Zijlstra, Jan J. Piek

Research output: Contribution to journalArticle

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Abstract

AimsThe 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 resultsWe 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.ConclusionIntracoronary 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. Published on behalf of the European Society of Cardiology. All rights reserved.

Original languageEnglish (US)
Pages (from-to)989-998
Number of pages10
JournalEuropean Heart Journal
Volume35
Issue number15
DOIs
StatePublished - 2014

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Cell- and Tissue-Based Therapy
Left Ventricular Function
Bone Marrow Cells
Meta-Analysis
Confidence Intervals
Stroke Volume
Randomized Controlled Trials
ST Elevation Myocardial Infarction
Ventricular Remodeling
Percutaneous Coronary Intervention
Therapeutics
Diabetes Mellitus
Arteries
Cell Count
Research Personnel

Keywords

  • Bone marrow cells
  • Meta-analysis
  • ST-segment elevation myocardial infarction
  • Ventricular function

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction : A collaborative meta-analysis. / Delewi, Ronak; Hirsch, Alexander; Tijssen, Jan G.; Schächinger, Volker; Wojakowski, Wojciech; Roncalli, Jérôme; Aakhus, Svend; Erbs, Sandra; Assmus, Birgit; Tendera, Michal; Goekmen Turan, R.; Corti, Roberto; Henry, Tim; Lemarchand, Patricia; Lunde, Ketil; Cao, Feng; Huikuri, Heikki V.; Sürder, Daniel; Simari, Robert D.; Janssens, Stefan; Wollert, Kai C.; Plewka, Michal; Grajek, Stefan; Traverse, Jay H.; Zijlstra, Felix; Piek, Jan J.

In: European Heart Journal, Vol. 35, No. 15, 2014, p. 989-998.

Research output: Contribution to journalArticle

Delewi, R, Hirsch, A, Tijssen, JG, Schächinger, V, Wojakowski, W, Roncalli, J, Aakhus, S, Erbs, S, Assmus, B, Tendera, M, Goekmen Turan, R, Corti, R, Henry, T, Lemarchand, P, Lunde, K, Cao, F, Huikuri, HV, Sürder, D, Simari, RD, Janssens, S, Wollert, KC, Plewka, M, Grajek, S, Traverse, JH, Zijlstra, F & Piek, JJ 2014, 'Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction: A collaborative meta-analysis', European Heart Journal, vol. 35, no. 15, pp. 989-998. https://doi.org/10.1093/eurheartj/eht372
Delewi, Ronak ; Hirsch, Alexander ; Tijssen, Jan G. ; Schächinger, Volker ; Wojakowski, Wojciech ; Roncalli, Jérôme ; Aakhus, Svend ; Erbs, Sandra ; Assmus, Birgit ; Tendera, Michal ; Goekmen Turan, R. ; Corti, Roberto ; Henry, Tim ; Lemarchand, Patricia ; Lunde, Ketil ; Cao, Feng ; Huikuri, Heikki V. ; Sürder, Daniel ; Simari, Robert D. ; Janssens, Stefan ; Wollert, Kai C. ; Plewka, Michal ; Grajek, Stefan ; Traverse, Jay H. ; Zijlstra, Felix ; Piek, Jan J. / Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction : A collaborative meta-analysis. In: European Heart Journal. 2014 ; Vol. 35, No. 15. pp. 989-998.
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abstract = "AimsThe 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 resultsWe 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.ConclusionIntracoronary 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. Published on behalf of the European Society of Cardiology. All rights reserved.",
keywords = "Bone marrow cells, Meta-analysis, ST-segment elevation myocardial infarction, Ventricular function",
author = "Ronak Delewi and Alexander Hirsch and Tijssen, {Jan G.} and Volker Sch{\"a}chinger and Wojciech Wojakowski and J{\'e}r{\^o}me Roncalli and Svend Aakhus and Sandra Erbs and Birgit Assmus and Michal Tendera and {Goekmen Turan}, R. and Roberto Corti and Tim Henry and Patricia Lemarchand and Ketil Lunde and Feng Cao and Huikuri, {Heikki V.} and Daniel S{\"u}rder and Simari, {Robert D.} and Stefan Janssens and Wollert, {Kai C.} and Michal Plewka and Stefan Grajek and Traverse, {Jay H.} and Felix Zijlstra and Piek, {Jan J.}",
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TY - JOUR

T1 - Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction

T2 - A collaborative meta-analysis

AU - Delewi, Ronak

AU - Hirsch, Alexander

AU - Tijssen, Jan G.

AU - Schächinger, Volker

AU - Wojakowski, Wojciech

AU - Roncalli, Jérôme

AU - Aakhus, Svend

AU - Erbs, Sandra

AU - Assmus, Birgit

AU - Tendera, Michal

AU - Goekmen Turan, R.

AU - Corti, Roberto

AU - Henry, Tim

AU - Lemarchand, Patricia

AU - Lunde, Ketil

AU - Cao, Feng

AU - Huikuri, Heikki V.

AU - Sürder, Daniel

AU - Simari, Robert D.

AU - Janssens, Stefan

AU - Wollert, Kai C.

AU - Plewka, Michal

AU - Grajek, Stefan

AU - Traverse, Jay H.

AU - Zijlstra, Felix

AU - Piek, Jan J.

PY - 2014

Y1 - 2014

N2 - AimsThe 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 resultsWe 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.ConclusionIntracoronary 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. Published on behalf of the European Society of Cardiology. All rights reserved.

AB - AimsThe 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 resultsWe 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.ConclusionIntracoronary 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. Published on behalf of the European Society of Cardiology. All rights reserved.

KW - Bone marrow cells

KW - Meta-analysis

KW - ST-segment elevation myocardial infarction

KW - Ventricular function

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