Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: The LateTIME randomized trial

Jay H. Traverse; Timothy D. Henry; Stephen G. Ellis; Carl J. Pepine; James T. Willerson; David X.M. Zhao; John R. Forder; Barry J. Byrne; Antonis K. Hatzopoulos; Marc S. Penn; Emerson C. Perin; Kenneth W. Baran; Jeffrey Chambers; Charles Lambert; Ganesh Raveendran; Daniel I. Simon; Douglas E. Vaughan; Lara M. Simpson; Adrian P. Gee; Doris A. Taylor; Christopher R. Cogle; James D. Thomas; Guilherme V. Silva; Beth C. Jorgenson; Rachel E. Olson; Sherry Bowman; Judy Francescon; Carrie Geither; Eileen Handberg; Deirdre X. Smith; Sarah Baraniuk; Linda B. Piller; Catalin Loghin; David Aguilar; Sara Richman; Claudia Zierold; Judy Bettencourt; Shelly L. Sayre; Rachel W. Vojvodic; Sonia I. Skarlatos; David J. Gordon; Ray F. Ebert; Minjung Kwak; Lemuel A. Moyé; Robert D. Simari

doi:10.1001/jama.2011.1670

Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: The LateTIME randomized trial

Jay H. Traverse, Timothy D. Henry, Stephen G. Ellis, Carl J. Pepine, James T. Willerson, David X.M. Zhao, John R. Forder, Barry J. Byrne, Antonis K. Hatzopoulos, Marc S. Penn, Emerson C. Perin, Kenneth W. Baran, Jeffrey Chambers, Charles Lambert, Ganesh Raveendran, Daniel I. Simon, Douglas E. Vaughan, Lara M. Simpson, Adrian P. Gee, Doris A. TaylorChristopher R. Cogle, James D. Thomas, Guilherme V. Silva, Beth C. Jorgenson, Rachel E. Olson, Sherry Bowman, Judy Francescon, Carrie Geither, Eileen Handberg, Deirdre X. Smith, Sarah Baraniuk, Linda B. Piller, Catalin Loghin, David Aguilar, Sara Richman, Claudia Zierold, Judy Bettencourt, Shelly L. Sayre, Rachel W. Vojvodic, Sonia I. Skarlatos, David J. Gordon, Ray F. Ebert, Minjung Kwak, Lemuel A. Moyé, Robert D. Simari

Cardiovascular Medicine

Research output: Contribution to journal › Article › peer-review

310 Scopus citations

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, because a substantial number of patients may not present for early cell delivery, the efficacy of autologous BMC delivery 2 to 3 weeks post-MI warrants investigation. Objective: To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2 to 3 weeks following first MI. Design, Setting, and Patients: A randomized, double-blind, placebo-controlled trial (LateTIME) of the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network of 87 patients with significant LV dysfunction (LV ejection fraction [LVEF] ≲γτ∀45%) following successful primary percutaneous coronary intervention (PCI) between July 8, 2008, and February 28, 2011. Interventions: Intracoronary infusion of 150 × 10⁶ autologous BMCs (total nucleated cells) or placebo (BMC:placebo, 2:1) was performed within 12 hours of bone marrow aspiration after local automated cell processing. Main Outcome Measures: Changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone between baseline and 6 months, measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volumes and infarct size. Results: A total of 87 patients were randomized (mean [SD] age, 57 [11] years; 83% men). Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible. Change between baseline and 6 months in the BMC group vs placebo for mean LVEF (48.7% to 49.2% vs 45.3% to 48.8%; between-group mean difference, -3.00; 95% CI, -7.05 to 0.95), wall motion in the infarct zone (6.2 to 6.5 mm vs 4.9 to 5.9 mm; between-group mean difference, -0.70; 95% CI, -2.78 to 1.34), and wall motion in the border zone (16.0 to 16.6 mm vs 16.1 to 19.3 mm; between-group mean difference, -2.60; 95% CI, -6.03 to 0.77) were not statistically significant. No significant change in LV volumes and infarct volumes was observed; both groups decreased by a similar amount at 6 months vs baseline. Conclusion: Among patients with MI and LV dysfunction following reperfusion with PCI, intracoronary infusion of autologous BMCs vs intracoronary placebo infusion, 2 to 3 weeks after PCI, did not improve global or regional function at 6 months. Trial Registration: clinicaltrials.gov Identifier: NCT00684060.

Original language	English (US)
Pages (from-to)	2110-2119
Number of pages	10
Journal	JAMA
Volume	306
Issue number	19
DOIs	https://doi.org/10.1001/jama.2011.1670
State	Published - Nov 16 2011

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General Medicine

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10.1001/jama.2011.1670

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Traverse, J. H., Henry, T. D., Ellis, S. G., Pepine, C. J., Willerson, J. T., Zhao, D. X. M., Forder, J. R., Byrne, B. J., Hatzopoulos, A. K., Penn, M. S., Perin, E. C., Baran, K. W., Chambers, J., Lambert, C., Raveendran, G., Simon, D. I., Vaughan, D. E., Simpson, L. M., Gee, A. P., ... Simari, R. D. (2011). Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: The LateTIME randomized trial. JAMA, 306(19), 2110-2119. https://doi.org/10.1001/jama.2011.1670

Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: The LateTIME randomized trial. / Traverse, Jay H.; Henry, Timothy D.; Ellis, Stephen G. et al.
In: JAMA, Vol. 306, No. 19, 16.11.2011, p. 2110-2119.

Research output: Contribution to journal › Article › peer-review

Traverse, JH, Henry, TD, Ellis, SG, Pepine, CJ, Willerson, JT, Zhao, DXM, Forder, JR, Byrne, BJ, Hatzopoulos, AK, Penn, MS, Perin, EC, Baran, KW, Chambers, J, Lambert, C, Raveendran, G, Simon, DI, Vaughan, DE, Simpson, LM, Gee, AP, Taylor, DA, Cogle, CR, Thomas, JD, Silva, GV, Jorgenson, BC, Olson, RE, Bowman, S, Francescon, J, Geither, C, Handberg, E, Smith, DX, Baraniuk, S, Piller, LB, Loghin, C, Aguilar, D, Richman, S, Zierold, C, Bettencourt, J, Sayre, SL, Vojvodic, RW, Skarlatos, SI, Gordon, DJ, Ebert, RF, Kwak, M, Moyé, LA & Simari, RD 2011, 'Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: The LateTIME randomized trial', JAMA, vol. 306, no. 19, pp. 2110-2119. https://doi.org/10.1001/jama.2011.1670

@article{65c9d83693c8464da4921d95de9bfda9,

title = "Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: The LateTIME randomized trial",

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, because a substantial number of patients may not present for early cell delivery, the efficacy of autologous BMC delivery 2 to 3 weeks post-MI warrants investigation. Objective: To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2 to 3 weeks following first MI. Design, Setting, and Patients: A randomized, double-blind, placebo-controlled trial (LateTIME) of the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network of 87 patients with significant LV dysfunction (LV ejection fraction [LVEF] ≲γτ∀45%) following successful primary percutaneous coronary intervention (PCI) between July 8, 2008, and February 28, 2011. Interventions: Intracoronary infusion of 150 × 106 autologous BMCs (total nucleated cells) or placebo (BMC:placebo, 2:1) was performed within 12 hours of bone marrow aspiration after local automated cell processing. Main Outcome Measures: Changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone between baseline and 6 months, measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volumes and infarct size. Results: A total of 87 patients were randomized (mean [SD] age, 57 [11] years; 83% men). Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible. Change between baseline and 6 months in the BMC group vs placebo for mean LVEF (48.7% to 49.2% vs 45.3% to 48.8%; between-group mean difference, -3.00; 95% CI, -7.05 to 0.95), wall motion in the infarct zone (6.2 to 6.5 mm vs 4.9 to 5.9 mm; between-group mean difference, -0.70; 95% CI, -2.78 to 1.34), and wall motion in the border zone (16.0 to 16.6 mm vs 16.1 to 19.3 mm; between-group mean difference, -2.60; 95% CI, -6.03 to 0.77) were not statistically significant. No significant change in LV volumes and infarct volumes was observed; both groups decreased by a similar amount at 6 months vs baseline. Conclusion: Among patients with MI and LV dysfunction following reperfusion with PCI, intracoronary infusion of autologous BMCs vs intracoronary placebo infusion, 2 to 3 weeks after PCI, did not improve global or regional function at 6 months. Trial Registration: clinicaltrials.gov Identifier: NCT00684060.",

author = "Traverse, {Jay H.} and Henry, {Timothy D.} and Ellis, {Stephen G.} and Pepine, {Carl J.} and Willerson, {James T.} and Zhao, {David X.M.} and Forder, {John R.} and Byrne, {Barry J.} and Hatzopoulos, {Antonis K.} and Penn, {Marc S.} and Perin, {Emerson C.} and Baran, {Kenneth W.} and Jeffrey Chambers and Charles Lambert and Ganesh Raveendran and Simon, {Daniel I.} and Vaughan, {Douglas E.} and Simpson, {Lara M.} and Gee, {Adrian P.} and Taylor, {Doris A.} and Cogle, {Christopher R.} and Thomas, {James D.} and Silva, {Guilherme V.} and Jorgenson, {Beth C.} and Olson, {Rachel E.} and Sherry Bowman and Judy Francescon and Carrie Geither and Eileen Handberg and Smith, {Deirdre X.} and Sarah Baraniuk and Piller, {Linda B.} and Catalin Loghin and David Aguilar and Sara Richman and Claudia Zierold and Judy Bettencourt and Sayre, {Shelly L.} and Vojvodic, {Rachel W.} and Skarlatos, {Sonia I.} and Gordon, {David J.} and Ebert, {Ray F.} and Minjung Kwak and Moy{\'e}, {Lemuel A.} and Simari, {Robert D.}",

year = "2011",

month = nov,

day = "16",

doi = "10.1001/jama.2011.1670",

language = "English (US)",

volume = "306",

pages = "2110--2119",

journal = "JAMA",

issn = "0098-7484",

publisher = "American Medical Association",

number = "19",

}

TY - JOUR

T1 - Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function

T2 - The LateTIME randomized trial

AU - Traverse, Jay H.

AU - Henry, Timothy D.

AU - Ellis, Stephen G.

AU - Pepine, Carl J.

AU - Willerson, James T.

AU - Zhao, David X.M.

AU - Forder, John R.

AU - Byrne, Barry J.

AU - Hatzopoulos, Antonis K.

AU - Penn, Marc S.

AU - Perin, Emerson C.

AU - Baran, Kenneth W.

AU - Chambers, Jeffrey

AU - Lambert, Charles

AU - Raveendran, Ganesh

AU - Simon, Daniel I.

AU - Vaughan, Douglas E.

AU - Simpson, Lara M.

AU - Gee, Adrian P.

AU - Taylor, Doris A.

AU - Cogle, Christopher R.

AU - Thomas, James D.

AU - Silva, Guilherme V.

AU - Jorgenson, Beth C.

AU - Olson, Rachel E.

AU - Bowman, Sherry

AU - Francescon, Judy

AU - Geither, Carrie

AU - Handberg, Eileen

AU - Smith, Deirdre X.

AU - Baraniuk, Sarah

AU - Piller, Linda B.

AU - Loghin, Catalin

AU - Aguilar, David

AU - Richman, Sara

AU - Zierold, Claudia

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 - 2011/11/16

Y1 - 2011/11/16

N2 - 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, because a substantial number of patients may not present for early cell delivery, the efficacy of autologous BMC delivery 2 to 3 weeks post-MI warrants investigation. Objective: To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2 to 3 weeks following first MI. Design, Setting, and Patients: A randomized, double-blind, placebo-controlled trial (LateTIME) of the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network of 87 patients with significant LV dysfunction (LV ejection fraction [LVEF] ≲γτ∀45%) following successful primary percutaneous coronary intervention (PCI) between July 8, 2008, and February 28, 2011. Interventions: Intracoronary infusion of 150 × 106 autologous BMCs (total nucleated cells) or placebo (BMC:placebo, 2:1) was performed within 12 hours of bone marrow aspiration after local automated cell processing. Main Outcome Measures: Changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone between baseline and 6 months, measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volumes and infarct size. Results: A total of 87 patients were randomized (mean [SD] age, 57 [11] years; 83% men). Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible. Change between baseline and 6 months in the BMC group vs placebo for mean LVEF (48.7% to 49.2% vs 45.3% to 48.8%; between-group mean difference, -3.00; 95% CI, -7.05 to 0.95), wall motion in the infarct zone (6.2 to 6.5 mm vs 4.9 to 5.9 mm; between-group mean difference, -0.70; 95% CI, -2.78 to 1.34), and wall motion in the border zone (16.0 to 16.6 mm vs 16.1 to 19.3 mm; between-group mean difference, -2.60; 95% CI, -6.03 to 0.77) were not statistically significant. No significant change in LV volumes and infarct volumes was observed; both groups decreased by a similar amount at 6 months vs baseline. Conclusion: Among patients with MI and LV dysfunction following reperfusion with PCI, intracoronary infusion of autologous BMCs vs intracoronary placebo infusion, 2 to 3 weeks after PCI, did not improve global or regional function at 6 months. Trial Registration: clinicaltrials.gov Identifier: NCT00684060.

AB - 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, because a substantial number of patients may not present for early cell delivery, the efficacy of autologous BMC delivery 2 to 3 weeks post-MI warrants investigation. Objective: To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2 to 3 weeks following first MI. Design, Setting, and Patients: A randomized, double-blind, placebo-controlled trial (LateTIME) of the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network of 87 patients with significant LV dysfunction (LV ejection fraction [LVEF] ≲γτ∀45%) following successful primary percutaneous coronary intervention (PCI) between July 8, 2008, and February 28, 2011. Interventions: Intracoronary infusion of 150 × 106 autologous BMCs (total nucleated cells) or placebo (BMC:placebo, 2:1) was performed within 12 hours of bone marrow aspiration after local automated cell processing. Main Outcome Measures: Changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone between baseline and 6 months, measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volumes and infarct size. Results: A total of 87 patients were randomized (mean [SD] age, 57 [11] years; 83% men). Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible. Change between baseline and 6 months in the BMC group vs placebo for mean LVEF (48.7% to 49.2% vs 45.3% to 48.8%; between-group mean difference, -3.00; 95% CI, -7.05 to 0.95), wall motion in the infarct zone (6.2 to 6.5 mm vs 4.9 to 5.9 mm; between-group mean difference, -0.70; 95% CI, -2.78 to 1.34), and wall motion in the border zone (16.0 to 16.6 mm vs 16.1 to 19.3 mm; between-group mean difference, -2.60; 95% CI, -6.03 to 0.77) were not statistically significant. No significant change in LV volumes and infarct volumes was observed; both groups decreased by a similar amount at 6 months vs baseline. Conclusion: Among patients with MI and LV dysfunction following reperfusion with PCI, intracoronary infusion of autologous BMCs vs intracoronary placebo infusion, 2 to 3 weeks after PCI, did not improve global or regional function at 6 months. Trial Registration: clinicaltrials.gov Identifier: NCT00684060.

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Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: The LateTIME randomized trial

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