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

Abstract

Context Clinical trial results suggest that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) may improve left ventricular (LV) function when administered within the first week following myocardial infarction (MI). However, since a substantial number of patients may not present for early cell delivery, we investigated the efficacy of autologous BMC delivery 2–3 weeks post-MI. Objective To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2–3 weeks following first MI. Design, Setting, and Patients LateTIME is a randomized, double-blind, placebo-controlled trial of the National Heart, Lung, and Blood Institute - sponsored Cardiovascular Cell Therapy Research Network (CCTRN) of 87 patients with significant LV dysfunction (LVEF ≤ 45%) following successful primary percutaneous coronary intervention (PCI). Interventions Intracoronary infusion of 150 × 106 autologous BMCs (total nucleated cells) or placebo (2:1 BMC:placebo) was performed within 12 hours of bone marrow aspiration after local automated cell processing. Main Outcome Measures The primary endpoints were changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone from baseline to 6 months as measured by cardiac MRI at a core lab blinded to treatment assignment Secondary endpoints included changes in LV volumes and infarct size. Results 87 patients were randomized between July 2008 and February 2011: mean age = 57 ± 11 yrs, 83% male. Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible and safe. The change from baseline to six months in the BMC group, when compared to the placebo group, for LVEF (48.7 to 49.2% vs. 45.3 to 48.8%; Difference = −3.0, 95% CI −7.0 to 0.9), wall motion in the infarct zone (6.2 to 6.5 vs. 4.9 to 5.9 mm; Difference = −0.7, 95% CI −2.8 to 1.3), and wall motion in the border zone (16.0 to 16.6 mm vs. 16.1 to 19.3 mm; Difference = −2.6; 95% CI −6.0 to 0.8) were not statistically significant. There was no significant change in LV volumes and infarct volumes decreased by a similar amount in both groups at 6 months compared to baseline. Conclusions Among patients with MI and LV dysfunction following reperfusion with PCI, intracoronary infusion of autologous BMCs compared to intracoronary placebo infusion, 2–3 weeks after PCI did not improve global or regional function at 6 months.

Stem Cell Therapy for Heart Disease

“…LateTIME showed negative results at 2-3 weeks. 60 MYS-TAR showed short-term increased EF, but no significant differences between treatment at 3-6 weeks and 3-4 months. 58 TIME, comparing BMC delivered on day 3 and day 7 after AMI, aimed to determine optimal timing.…”

“…52 REPAIR-AMI and TOP-CARE-AMI confirmed that patients with decreased baseline EF showed more improvement. 44,45,51,52 Some trials did not show significant results, 57,60,[63][64][65] while others demonstrated some benefits without EF changes. 43,53,54,62 Heart Failure Additionally, there have been multiple HF trials (Table 2).…”

Prompt Bone Marrow-Derived Mesenchymal Stem Cell Therapy Enables Early Porcine Heart Function Recovery from Acute Myocardial Infarction

“…However, practically, because early cell delivery may not be possible for the majority of patients, the efficacy of autologous BM-DMNC delivery at either 3 days or 7 days or 2 to 3 weeks post-MI has been investigated by the TIME randomized trial 16) and the Late TIME randomized trial. 15) The results of these studies demonstrated that intracoronary infusion of autologous BMDMNCs or placebo at these time points after PCI did not improve global or regional function after 6 months. 15) Recently, an open-labeled control clinical trial has also demonstrated that, among patients with AMI and LV dysfunction following successful reperfusion, intracoronary infusion of BMDMNC at either 5-7 days or 3-4 weeks after AMI did not improve LVfunction at 4-month follow-up.…”

“…15) The results of these studies demonstrated that intracoronary infusion of autologous BMDMNCs or placebo at these time points after PCI did not improve global or regional function after 6 months. 15) Recently, an open-labeled control clinical trial has also demonstrated that, among patients with AMI and LV dysfunction following successful reperfusion, intracoronary infusion of BMDMNC at either 5-7 days or 3-4 weeks after AMI did not improve LVfunction at 4-month follow-up. 44) The particularly noteworthy finding in the present study is that rapid implantation of BM-DMSC significantly improved the heart function after permanent AMI in the mini-pig model.…”

“…[6][7][8][9] Indeed, some studies have reported that SC therapy exhibited only temporary 5,8,9) or minimal 10) effectiveness, or was even ineffective [11][12][13][14][15][16] in improving global LV ejection fraction (LVEF) in patients after acute myocardial infarction (AMI). Further analysis of these clinical trials revealed that stem cell therapy was performed only several days after 5,8,9,[11][12][13] rather than immediately after AMI.…”