[Physician Comment] Autologous bone marrow cell infusion following myocardial infarction elicits no improvement in left ventricular function

Image: CC/P.Lynch

Study author, Dr. Jay Traverse, M.D. talks to 2 Minute Medicine *Senior cardiology associate at the Minneapolis Heart Institute® at Abbott Northwestern Hospital and an Associate Professor of Medicine in the Department of Cardiology at the University of Minnesota

“The timing of stem cell delivery following myocardial infarction has never been prospectively analyzed and may be important in determining efficacy given the changes in heart and bone marrow that occur shortly after MI. We performed a randomized, placebo-controlled, trial of 120 patients with mod-large anterior STEMIs with significant LV dysfxn (LVEF < 45%) who were randomized to cell therapy / placebo on either Day 3 or Day 7 following successful primary PCI. We observed that bone marrow mononuclear cell therapy did not augment the recovery of global or regional LV function at 6 months as measured by cardiac MRI. There were no safety issues associated with the therapy.”

Key study points:

1. Intracoronary infusion of autologous bone marrow cells versus placebo; at either day 3 or 7 after a ST-segment elevation myocardial infarction (STEMI) did not show significant improvement in left ventricular function at six months.

Primer: Myocardial infarctions (MI) result from the interruption of vascular flow through the coronary arteries of the heart. This most commonly occurs secondary to vulnerable atherosclerotic plaques that spontaneously rupture occluding the distal vasculature. The resulting myocardial ischemia, if left untreated, can cause irreversible damage or death of the heart muscle. Currently, regardless of mechanical reperfusion techniques or pharmacologic therapy, the infarcted myocardium mainly heals by scar formation. In this setting, it has been hypothesized that the infusion of bone marrow stem cells (BMCs) into infarcted myocardium could instead allow for healing by regeneration with the desired result of improved contractile function. In a previous study, the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial showed improved left ventricular function in patients infused with BMCs 5-7 days after an MI. However, in this current study, the researchers sought to randomly select the day of infusion in order to determine whether the timing of intracoronary bone marrow cell infusion demonstrated an improvement left ventricular function in short-term follow up.

Background reading:

1. Up-to-Date: Genetic and Cellular Therapy in Heart Failure and Myocardial Infarction

2. Stem Cell Treatment for Acute Myocardial Infarction

3. Effect of Intracoronary Delivery of Autologous Bone Marrow Mononuclear Cells 2 to 3 Weeks Following Acute Myocardial Infarction on Left Ventricular Function

4. Intracoronary Injection of Mononuclear Bone Marrow Cells in Acute Myocardial Infarction

This [randomized, double-blind, placebo-controlled] study:  The study enrolled 120 patients who experienced a STEMI. All patients included in the trial underwent percutaneous coronary intervention (PCI) and had a resulting left ventricular ejection fraction (LVEF) of 45% or. Patients were randomized to receive therapy on either day 3 or 7 after PCI and then secondarily randomized to receive autologous bone marrow cells (BMCs) or placebo. The primary end points centered on ventricular function. In the day both day 3 and 7 groups, there were no differences in left ventricular function at 6 months between BMCs and placebo. Overall, at 6 months, in both BMC groups combined (day 3 and day 7) the LVEF increased from 45.2% at baseline to 48.3% at 6 months compared to 44.5% at baseline and 47.8% for the combined placebo groups.

In sum: The authors of this randomized, 2×2 factorial, double-blind, placebo-controlled study demonstrated that the timing intracoronary infusion of autologous bone marrow cells showed no significant improvement in left ventricular ejection fraction or in infarct zone wall motion at six months. The outcome of this study was surprising as a Cochrane review released in February of 2012 concluded there to be moderate improvement of global heart function with long-term follow up in patients who received BMC infusions. Given the sample size of 130 patients, it may be too small of a cohort to truly identify a significant difference. Also, there is likely considerable heterogeneity in the composition and regenerative capacity of the BMC products from individual patients. As one possibility, perhaps enriching the bone marrow products from patients for certain stem cell lineages specific for cardiac myocytes would also improve outcomes. While this study did not show a significant difference in left ventricular function at six months it is possible that long-term would yield a more positive result. Nonetheless, it provides an interesting result which will hopefully raise the need for further study in the use and development of novel stem cell therapies for myocardial ischemia.

Click to read the study in JAMA

By [BH] and [RR]

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