DALLAS — Infusion of bone marrow progenitor cells into a coronary artery after a myocardial infarction led to significantly improved left ventricular function in a controlled study with almost 200 patients.
“This is the first large, proof-of-concept trial to clearly show the benefit of progenitor cells in post-myocardial infarction patients,” Dr. Volker Schächinger said at the annual scientific sessions of the American Heart Association.
“Large-scale clinical-end point trials are now needed to assess the effect of intracoronary infusion of bone marrow cells on morbidity and mortality in patients,” said Dr. Schächinger, professor of medicine at J.W. Goethe University in Frankfurt.
“The data give compelling evidence of the treatment's benefit,” but the new findings conflict with a prior report from Belgian researchers that failed to show increased ventricular function following similar treatment, commented Dr. Philippe Menasche, a cardiovascular surgeon at the Georges Pompidou European Hospital in Paris. Because of these conflicting findings, “additional, large-scale trials are warranted to clarify the efficacy issue,” he said.
The study enrolled 204 patients who had an ST-segment elevation MI and were successfully reperfused with either a percutaneous coronary intervention or a thrombolytic drug. The study was done at 16 medical centers in Germany and one in Switzerland. At 3–6 days following the MI, 50 mL of bone marrow was aspirated from each patient and filtered through a ficoll gradient to enrich for progenitor cells, which takes about 90 minutes.
Patients then received an infusion into their infarct-related artery of either the progenitor cells in growth medium, or the medium with no cells, as a control. An average of 236 million cells were infused into each patient who received bone-marrow cells. The cells were introduced with a stop-flow catheter that briefly halted blood flow within the treated artery. Left ventricular ejection fraction (LVEF) was measured at the time of treatment and 4 months later, using left-ventricular angiography.
During follow-up, LVEF increased by an average of 3% over baseline in 92 evaluable control patients and by an average of 5.5% in 95 evaluable patients who received bone marrow cells, a statistically significant effect for the study's primary end point, Dr. Schächinger said.
Two additional analyses were done to identify conditions that were linked to the best outcomes. One divided the patients into the 93 evaluable patients who had an LVEF of less than 49% at baseline and the 94 evaluable patients with LVEF of 49% or greater at baseline.
Among the patients with LVEF of less than 49%, treatment with bone marrow cells led to an average 7.5% boost in LVEF, compared with an average 2.5% improvement in control patients, a statistically significant difference. In patients who had LVEF of 49% or greater at baseline cell treatment led to no significant improvement, compared with the controls.
The other exploratory analysis divided patients based on when they were treated following their MI. Patients who received cell treatment 5 or more days after their infarction had an average 7.0% increase in LVEF, compared with an average 1.9% increase among control patients, a significant difference. Patients treated less than 5 days after their infarction did not have a significant improvement, compared with the controls.
The researchers aren't sure why patients responded better if treatment was delayed a few days. “Early after a myocardial infarction, the myocardium is a hostile environment, with inflammation and oxidative stress. That may be why it's better to delay treatment,” Dr. Schächinger said. “We can't draw conclusions now regarding the mechanism of what's happening. But regardless of the mechanism, we clearly showed a benefit that's better than placebo.”
“The data are spectacular. They not only showed a positive result, but they identified the patients who got the most benefit,” said Dr. Andreas M. Zeiher, professor and chief of cardiology at Goethe University and senior investigator for the study. The Frankfurt researchers are now planning to do a study with about 1,200 patients that will focus on treating patients with an LVEF of less than 50%, and with marrow cell treatment delayed until at least 6 days following an MI, Dr. Zeiher said in an interview.