TY - JOUR
T1 - Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction
T2 - The time randomized trial
AU - Traverse, Jay H.
AU - Henry, Timothy D.
AU - Pepine, Carl J.
AU - Willerson, James T.
AU - Zhao, David X.M.
AU - Ellis, Stephen G.
AU - Forder, John R.
AU - Anderson, R. David
AU - Hatzopoulos, Antonis K.
AU - Penn, Marc S.
AU - Perin, Emerson C.
AU - Chambers, Jeffrey
AU - Baran, Kenneth W.
AU - Raveendran, Ganesh
AU - Lambert, Charles
AU - Lerman, Amir
AU - Simon, Daniel I.
AU - Vaughan, Douglas E.
AU - Lai, Dejian
AU - Gee, Adrian P.
AU - Taylor, Doris A.
AU - Cogle, Christopher R.
AU - Thomas, James D.
AU - Olson, Rachel E.
AU - Bowman, Sherry
AU - Francescon, Judy
AU - Geither, Carrie
AU - Handberg, Eileen
AU - Kappenman, Casey
AU - Westbrook, Lynette
AU - Piller, Linda B.
AU - Simpson, Lara M.
AU - Baraniuk, Sarah
AU - Loghin, Catalin
AU - Aguilar, David
AU - Richman, Sara
AU - Zierold, Claudia
AU - Spoon, Daniel B.
AU - Bettencourt, Judy
AU - Sayre, Shelly L.
AU - Vojvodic, Rachel W.
AU - Skarlatos, Sonia I.
AU - Gordon, David J.
AU - Ebert, Ray F.
AU - Kwak, Minjung
AU - Moyé, Lemuel A.
AU - Simari, Robert D.
PY - 2012/12/12
Y1 - 2012/12/12
N2 - Context: While the delivery of cell therapy after ST-segment elevation myocardial infarction (STEMI) has been evaluated in previous clinical trials, the influence of the timing of cell delivery on the effect on left ventricular function has not been analyzed. Objectives: To determine the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery after STEMI on recovery of global and regional left ventricular function and whether timing of BMC delivery (3 days vs 7 days after reperfusion) influences this effect. Design, Setting, and Patients: A randomized, 2 x 2 factorial, double-blind, placebo-controlled trial, Timing In Myocardial infarction Evaluation (TIME) enrolled 120 patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤45%) after successful primary percutaneous coronary intervention (PCI) of anterior STEMI between July 17, 2008, and November 15, 2011, as part of the Cardiovascular Cell Therapy Research Network sponsored by the National Heart, Lung, and Blood Institute. Interventions: Intracoronary infusion of 150 × 106 BMCs or placebo (randomized 2:1) within 12 hours of aspiration and cell processing administered at day 3 or day 7 (randomized 1:1) after treatment with PCI. Main Outcome Measures: The primary end points were change in global (LVEF) and regional (wall motion) left ventricular function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging and change in left ventricular function as affected by timing of treatment on day 3 vs day 7. The secondary end points included major adverse cardiovascular events as well as changes in left ventricular volumes and infarct size. Results: The mean (SD) patient age was 56.9 (10.9) years and 87.5% of participants were male. At 6 months, there was no significant increase in LVEF for the BMC group (45.2% [95% CI, 42.8% to 47.6%] to 48.3% [95% CI, 45.3% to 51.3%) vs the placebo group (44.5% [95% CI, 41.0% to 48.0%] to 47.8% [95% CI, 43.4% to 52.2%]) (P=.96). There was no significant treatment effect on regional left ventricular function observed in either infarct or border zones. There were no significant differences in change in global left ventricular function for patients treated at day 3 (-0.9% [95% CI, -6.6% to 4.9%], P=.76) or day 7 (1.1% [95% CI, -4.7% to 6.9%], P=.70). The timing of treatment had no significant effect on regional left ventricular function recovery. Major adverse events were rare among all treatment groups. Conclusion: Among patients with STEMI treated with primary PCI, the administration of intracoronary BMCs at either 3 days or 7 days after the event had no significant effect on recovery of global or regional left ventricular function compared with placebo. Trial Registration: clinicaltrials.gov Identifier: NCT00684021.
AB - Context: While the delivery of cell therapy after ST-segment elevation myocardial infarction (STEMI) has been evaluated in previous clinical trials, the influence of the timing of cell delivery on the effect on left ventricular function has not been analyzed. Objectives: To determine the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery after STEMI on recovery of global and regional left ventricular function and whether timing of BMC delivery (3 days vs 7 days after reperfusion) influences this effect. Design, Setting, and Patients: A randomized, 2 x 2 factorial, double-blind, placebo-controlled trial, Timing In Myocardial infarction Evaluation (TIME) enrolled 120 patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤45%) after successful primary percutaneous coronary intervention (PCI) of anterior STEMI between July 17, 2008, and November 15, 2011, as part of the Cardiovascular Cell Therapy Research Network sponsored by the National Heart, Lung, and Blood Institute. Interventions: Intracoronary infusion of 150 × 106 BMCs or placebo (randomized 2:1) within 12 hours of aspiration and cell processing administered at day 3 or day 7 (randomized 1:1) after treatment with PCI. Main Outcome Measures: The primary end points were change in global (LVEF) and regional (wall motion) left ventricular function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging and change in left ventricular function as affected by timing of treatment on day 3 vs day 7. The secondary end points included major adverse cardiovascular events as well as changes in left ventricular volumes and infarct size. Results: The mean (SD) patient age was 56.9 (10.9) years and 87.5% of participants were male. At 6 months, there was no significant increase in LVEF for the BMC group (45.2% [95% CI, 42.8% to 47.6%] to 48.3% [95% CI, 45.3% to 51.3%) vs the placebo group (44.5% [95% CI, 41.0% to 48.0%] to 47.8% [95% CI, 43.4% to 52.2%]) (P=.96). There was no significant treatment effect on regional left ventricular function observed in either infarct or border zones. There were no significant differences in change in global left ventricular function for patients treated at day 3 (-0.9% [95% CI, -6.6% to 4.9%], P=.76) or day 7 (1.1% [95% CI, -4.7% to 6.9%], P=.70). The timing of treatment had no significant effect on regional left ventricular function recovery. Major adverse events were rare among all treatment groups. Conclusion: Among patients with STEMI treated with primary PCI, the administration of intracoronary BMCs at either 3 days or 7 days after the event had no significant effect on recovery of global or regional left ventricular function compared with placebo. Trial Registration: clinicaltrials.gov Identifier: NCT00684021.
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U2 - 10.1001/jama.2012.28726
DO - 10.1001/jama.2012.28726
M3 - Article
C2 - 23129008
AN - SCOPUS:84870877380
SN - 0098-7484
VL - 308
SP - 2380
EP - 2389
JO - JAMA
JF - JAMA
IS - 22
ER -