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] ≤45%) following successful primary percutaneous coronary intervention (PCI) between July 8, 2008, and February 28, 2011. INTERVENTIONS: Intracoronary infusion of 150 × 10(6) 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 withPCI, 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.
RCT Entities:
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] ≤45%) following successful primary percutaneous coronary intervention (PCI) between July 8, 2008, and February 28, 2011. INTERVENTIONS: Intracoronary infusion of 150 × 10(6) 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.
Authors: Alexander Hirsch; Robin Nijveldt; Pieter A van der Vleuten; Jan G P Tijssen; Willem J van der Giessen; René A Tio; Johannes Waltenberger; Jurrien M ten Berg; Pieter A Doevendans; Wim R M Aengevaeren; Jaap Jan Zwaginga; Bart J Biemond; Albert C van Rossum; Jan J Piek; Felix Zijlstra Journal: Eur Heart J Date: 2010-12-10 Impact factor: 29.983
Authors: Robert D Simari; Lemuel A Moyé; Sonia I Skarlatos; Stephen G Ellis; David X M Zhao; James T Willerson; Timothy D Henry; Carl J Pepine Journal: J Cardiovasc Transl Res Date: 2010-02 Impact factor: 4.132
Authors: S Shintani; T Murohara; H Ikeda; T Ueno; T Honma; A Katoh; K Sasaki; T Shimada; Y Oike; T Imaizumi Journal: Circulation Date: 2001-06-12 Impact factor: 29.690
Authors: Volker Schächinger; Sandra Erbs; Albrecht Elsässer; Werner Haberbosch; Rainer Hambrecht; Hans Hölschermann; Jiangtao Yu; Roberto Corti; Detlef G Mathey; Christian W Hamm; Tim Süselbeck; Birgit Assmus; Torsten Tonn; Stefanie Dimmeler; Andreas M Zeiher Journal: N Engl J Med Date: 2006-09-21 Impact factor: 91.245
Authors: Jay H Traverse; Timothy D Henry; Douglas E Vaughan; Stephen G Ellis; Carl J Pepine; James T Willerson; David X M Zhao; Lara M Simpson; Marc S Penn; Barry J Byrne; Emerson C Perin; Adrian P Gee; Antonis K Hatzopoulos; David H McKenna; John R Forder; Doris A Taylor; Christopher R Cogle; Sarah Baraniuk; Rachel E Olson; Beth C Jorgenson; Shelly L Sayre; Rachel W Vojvodic; David J Gordon; Sonia I Skarlatos; Lemuel A Moyè; Robert D Simari Journal: Tex Heart Inst J Date: 2010
Authors: Jay H Traverse; David H McKenna; Karen Harvey; Beth C Jorgenso; Rachel E Olson; Nancy Bostrom; Diane Kadidlo; John R Lesser; Vikrant Jagadeesan; Ross Garberich; Timothy D Henry Journal: Am Heart J Date: 2010-09 Impact factor: 4.749
Authors: James D Richardson; Adam J Nelson; Andrew C W Zannettino; Stan Gronthos; Stephen G Worthley; Peter J Psaltis Journal: Stem Cell Rev Rep Date: 2013-06 Impact factor: 5.739
Authors: Robert D Simari; Carl J Pepine; Jay H Traverse; Timothy D Henry; Roberto Bolli; Daniel B Spoon; Ed Yeh; Joshua M Hare; Ivonne Hernandez Schulman; R David Anderson; Charles Lambert; Shelly L Sayre; Doris A Taylor; Ray F Ebert; Lemuel A Moyé Journal: Circ Res Date: 2014-05-09 Impact factor: 17.367