Elsevier

The Lancet

Volume 364, Issue 9429, 10–16 July 2004, Pages 141-148
The Lancet

Articles
Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial

https://doi.org/10.1016/S0140-6736(04)16626-9Get rights and content

Summary

Background

Emerging evidence suggests that stem cells and progenitor cells derived from bone marrow can be used to improve cardiac function in patients after acute myocardial infarction. In this randomised trial, we aimed to assess whether intracoronary transfer of autologous bone-marrow cells could improve global left-ventricular ejection fraction (LVEF) at 6 months' follow-up.

Methods

After successful percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction, 60 patients were randomly assigned to either a control group (n=30) that received optimum postinfarction medical treatment, or a bone-marrow-cell group (n=30) that received optimum medical treatment and intracoronary transfer of autologous bone-marrow cells 4·8 days (SD 1·3) after PCI. Primary endpoint was global left-ventricular ejection fraction (LVEF) change from baseline to 6 months' follow-up, as determined by cardiac MRI. Image analyses were done by two investigators blinded for treatment assignment. Analysis was per protocol.

Findings

Global LVEF at baseline (determined 3·5 days [SD 1·5] after PCI) was 51·3 (9·3%) in controls and 50·0 (10·0%) in the bone-marrow cell group (p=0·59). After 6 months, mean global LVEF had increased by 0·7 percentage points in the control group and 6·7 percentage points in the bone-marrow-cell group (p=0·0026). Transfer of bone-marrow cells enhanced left-ventricular systolic function primarily in myocardial segments adjacent to the infarcted area. Cell transfer did not increase the risk of adverse clinical events, in stent restenosis, or proarrhythmic effects.

Interpretation

Intracoronary transfer of autologous bone-marrow-cells promotes improvement of left-ventricular systolic function in patients after acute myocardial infarction.

Introduction

Rapid reperfusion of the infarct-related coronary artery is of great importance in salvaging ischaemic myocardium and limiting the infarct size in patients with acute myocardial infarction. When done expeditiously and expertly, percutaneous transluminal coronary angioplasty with stent implantation is the method of choice to re-establish coronary flow.1 Unfortunately, myocardial necrosis starts rapidly after coronary occlusion, usually before reperfusion can be achieved.2 The loss of viable myocardium initiates a process of adverse left-ventricular remodelling, leading to chamber dilatation and contractile dysfunction in many patients.3 In this context, much interest has followed from experimental studies showing that cardiac transfer of unfractionated bone-marrow cells, or stem cells and progenitor cells derived from bone marrow can enhance functional recovery after acute myocardial infarction.4, 5 Based on these data, stem cells and progenitor cells derived from bone marrow have been proposed for use in the repair of cardiac tissue after acute myocardial infarction in patients.6, 7, 8

Early clinical investigations indicate that infusion of autologous bone-marrow cells into the infarct-related coronary artery is feasible after acute myocardial infarction.9, 10 However, because these studies were not randomised trials, the efficacy of intracoronary transfer of bone-marrow cells for functional recovery after acute myocardial infarction in patients has remained uncertain. We did a randomised controlled trial to assess the effect of intracoronary transfer of autologous bone-marrow cells on left-ventricular functional recovery in patients after acute myocardial infarction and successful percutaneous coronary intervention (PCI).

Section snippets

Patients

Patients were eligible if they were admitted within 5 days of the onset of symptoms of a first ST-segment elevation myocardial infarction, had undergone successful PCI with stent implantation in the infarct-related artery, and had hypokinesia or akinesia involving more than two thirds of the left-ventricular anteroseptal, lateral, and/or inferior wall, as shown by angiography done immediately after PCI. We excluded patients who had multivessel coronary artery disease, pulmonary oedema,

Results

Between January, 2002, and May, 2003, 78 patients were informed about the trial. 65 patients were randomly allocated to treatment. After randomisation, five patients were withdrawn because they could not undergo cardiac MRI, either because of claustrophobia or severe obesity. The final cohort included 30 controls and 30 patients in the bone-marrow-cell group (figure 1). Table 1 shows patients' baseline characteristics. All patients received optimum postinfarction medical treatment (table 1).

Discussion

Our randomised controlled clinical trial addresses the effect of autologous bone-marrow-cell therapy on left-ventricular functional recovery after acute ST-segment elevation myocardial infarction. We have shown that infusion of autologous bone-marrow-cells into the infarct-related coronary artery during the early postinfarction period (4–8 days after symptom onset) improves recovery of global LVEF after 6 months.

In view of the size of our trial, subgroup analyses must be considered with

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