Cell therapy delivered either three or seven days after STEMI failed to improve heart function, according to a study presented Nov. 6 at the American Heart Association’s (AHA) scientific sessions in Los Angeles and simultaneously published online in the Journal of the America Medical Association.
The study was conducted through the Cardiovascular Cell Therapy Research Network, which was set up by the National Heart, Lung and Blood Institute to investigate cardiovascular cell therapy with trials such as LateTIME. In 2011, LateTIME researchers reported no global or regional left ventricular (LV) functional improvements at six months in patients with MI and LV dysfunction who were administered autologous bone marrow mononuclear cells (BMCs) two to three weeks after PCI (JAMA 2011;306:2110-2119). The study was led by Jay H. Traverse, MD, of the Minneapolis Heart Institute.
In a companion randomized, double-blind, placebo-controlled trial, Traverse and colleagues designed TIME (Transplantation in MI Evaluation) to explore if and how timing of the delivery of BMC within the first week after MI affected LV function six months after PCI. Timing of treatment was set at three and seven days.
TIME enrolled 120 high-risk STEMI patients between July 2008 and November 2011 with an LV ejection fraction of 45 percent or less after PCI, randomized to one of four groups: at day three receiving BMCs; at day three receiving placebo; at day seven receiving BMCs; and at day seven receiving placebo. There were few significant differences between the patient groups.
Primary endpoints were change in global and regional LV function (measured by MRI) between baseline and six months and change in LV function based on the timing of treatment. Secondary endpoints included major adverse cardiovascular events and LV volumes and infarct size.
Traverse and colleagues reported no differences at six months between the BMC groups and placebo groups, and no significant differences by timing of treatment. In all groups, major adverse cardiovascular events were rare.
“There was no overall effect of BMC treatment on this ongoing improvement at six months vs. placebo despite previous supportive clinical data,” they wrote. “Additionally, the day of cell delivery did not demonstrate an effect on the recovery of left ventricular function or on left ventricular volumes or infarct size.”
They noted the challenges of identifying patients who met their inclusion criteria, given that contemporary practice that is both swift and aggressive. Participating centers screened more than 3,000 patients, of whom only 134 qualified.
They suggested alternative approaches may be needed, such as recruiting patients with demonstrated incomplete recovery at later time points. Other factors that may have influenced their results may include the possibility that BMCs from these patients may have less regenerative capacity than from healthy people.
“Although the field of cell therapy in cardiovascular disease has potential for identifying beneficial treatments, our study is consistent with the possibility that BMCs are not effective at improving left ventricular function when delivered into the immediate post-STEMI myocardial environment,” Traverse et al concluded. “However, long-term follow-up of these patients and the development of new composite endpoints may still reveal a role for this cell type after AMI.”