Effect of the Use and Timing of Bone Marrow Mononuclear Cell Delivery on Left Ventricular Function After Acute Myocardial Infarction: The TIME Randomized Trial

Study Questions:

What is the optimal timing for treatment with bone-marrow mononuclear cells (BMCs) for improvement of left ventricular (LV) function following myocardial infarction (MI)?


In the TIME (Timing in Myocardial Infarction Evaluation) trial, 120 patients with LV dysfunction (ejection fraction [EF] ≤45%) after successful percutaneous coronary intervention (PCI) of anterior ST-segment elevation MI (STEMI) were randomized to receive intracoronary infusion of 150 x 106 BMCs or placebo at day 3 or 7 following PCI. Outcomes at 6 months included change in EF, wall motion, infarct size, chamber size—all measured by magnetic resonance imaging, and cardiovascular events.


At 6 months, there was no significant increase in LVEF for the BMC group (45.2% to 48.3%) versus the placebo group (44.5% to 47.8%) (p = 0.96). No treatment effect on regional LV function was observed in either infarct or border zones, and there were no differences in change in global LV function for patients treated at day 3 or day 7.


The authors concluded that among patients with STEMI treated with primary PCI, the administration of intracoronary BMCs at either day 3 or day 7 after the event had no significant effect on recovery of global or regional LV function compared with placebo.


The effectiveness of cell-based therapy for recovery of myocardium following MI is controversial. The REPAIR-AMI trial demonstrated that treatment with BMC at 5-7 days following MI was more effective than earlier treatment. This TIME trial prospectively addressed the possibility that differences in the timing of treatment would affect outcome. Unfortunately, there was no beneficial effect of BMCs at either time point. It appears that further refinement of strategies will be necessary for this field to advance.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Myocardial Infarction, Bone Marrow Cells, Percutaneous Coronary Intervention

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