TY - JOUR
T1 - Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy
T2 - The TAC-HFT randomized trial
AU - Heldman, Alan W.
AU - DiFede, Darcy L.
AU - Fishman, Joel E.
AU - Zambrano, Juan P.
AU - Trachtenberg, Barry H.
AU - Karantalis, Vasileios
AU - Mushtaq, Muzammil
AU - Williams, Adam R.
AU - Suncion, Viky Y.
AU - McNiece, Ian K.
AU - Ghersin, Eduard
AU - Soto, Victor
AU - Lopera, Gustavo
AU - Miki, Roberto
AU - Willens, Howard
AU - Hendel, Robert
AU - Mitrani, Raul
AU - Pattany, Pradip
AU - Feigenbaum, Gary
AU - Oskouei, Behzad
AU - Byrnes, John
AU - Lowery, Maureen H.
AU - Sierra, Julio
AU - Pujol, Mariesty V.
AU - Delgado, Cindy
AU - Gonzalez, Phillip J.
AU - Rodriguez, Jose E.
AU - Bagno, Luiza Lima
AU - Rouy, Didier
AU - Altman, Peter
AU - Foo, Cheryl Wong Po
AU - Da Silva, Jose
AU - Anderson, Erica
AU - Schwarz, Richard
AU - Mendizabal, Adam
AU - Hare, Joshua M.
PY - 2014
Y1 - 2014
N2 - IMPORTANCE: Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial. OBJECTIVE: To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy. DESIGN, SETTING, AND PATIENTS: A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than50%(September 1, 2009-July 12, 2013). The study compared injection of MSCs (n=19) with placebo (n = 11) and BMCs (n = 19) with placebo (n = 10), with 1 year of follow-up. INTERVENTIONS: Injections in 10 LV sites with an infusion catheter. MAIN OUTCOMES AND MEASURES: Treatment-emergent 30-day serious adverse event rate defined as a composite of death, myocardial infarction, stroke, hospitalization for worsening heart failure, perforation, tamponade, or sustained ventricular arrhythmias. RESULTS: No patient had a treatment-emergent serious adverse events at day 30. The 1-year incidence of serious adverse events was 31.6%(95%CI, 12.6%to 56.6%) for MSCs, 31.6% (95%CI, 12.6%-56.6%) for BMCs, and 38.1%(95%CI, 18.1%-61.6%) for placebo. Over 1 year, the Minnesota Living With Heart Failure score improved with MSCs (-6.3; 95%CI, -15.0 to 2.4; repeated measures of variance, P=.02) and with BMCs (-8.2; 95%CI, -17.4 to 0.97; P=.005) but not with placebo (0.4; 95%CI, -9.45 to 10.25; P=.38). The 6-minute walk distance increased with MSCs only (repeated measures model, P = .03). Infarct size as a percentage of LV mass was reduced by MSCs (-18.9%; 95%CI, -30.4 to -7.4; within-group, P = .004) but not by BMCs (-7.0%; 95%CI, -15.7%to 1.7%; within-group, P = .11) or placebo (-5.2%; 95%CI, -16.8%to 6.5%; within-group, P = .36). Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs (-4.9; 95%CI, -13.3 to 3.5; within-group repeated measures, P = .03) but not BMCs (-2.1; 95%CI, -5.5 to 1.3; P = .21) or placebo (-0.03; 95%CI, -1.9 to 1.9; P = .14). Left ventricular chamber volume and ejection fraction did not change. CONCLUSIONS AND RELEVANCE: Transendocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction. Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00768066
AB - IMPORTANCE: Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial. OBJECTIVE: To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy. DESIGN, SETTING, AND PATIENTS: A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than50%(September 1, 2009-July 12, 2013). The study compared injection of MSCs (n=19) with placebo (n = 11) and BMCs (n = 19) with placebo (n = 10), with 1 year of follow-up. INTERVENTIONS: Injections in 10 LV sites with an infusion catheter. MAIN OUTCOMES AND MEASURES: Treatment-emergent 30-day serious adverse event rate defined as a composite of death, myocardial infarction, stroke, hospitalization for worsening heart failure, perforation, tamponade, or sustained ventricular arrhythmias. RESULTS: No patient had a treatment-emergent serious adverse events at day 30. The 1-year incidence of serious adverse events was 31.6%(95%CI, 12.6%to 56.6%) for MSCs, 31.6% (95%CI, 12.6%-56.6%) for BMCs, and 38.1%(95%CI, 18.1%-61.6%) for placebo. Over 1 year, the Minnesota Living With Heart Failure score improved with MSCs (-6.3; 95%CI, -15.0 to 2.4; repeated measures of variance, P=.02) and with BMCs (-8.2; 95%CI, -17.4 to 0.97; P=.005) but not with placebo (0.4; 95%CI, -9.45 to 10.25; P=.38). The 6-minute walk distance increased with MSCs only (repeated measures model, P = .03). Infarct size as a percentage of LV mass was reduced by MSCs (-18.9%; 95%CI, -30.4 to -7.4; within-group, P = .004) but not by BMCs (-7.0%; 95%CI, -15.7%to 1.7%; within-group, P = .11) or placebo (-5.2%; 95%CI, -16.8%to 6.5%; within-group, P = .36). Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs (-4.9; 95%CI, -13.3 to 3.5; within-group repeated measures, P = .03) but not BMCs (-2.1; 95%CI, -5.5 to 1.3; P = .21) or placebo (-0.03; 95%CI, -1.9 to 1.9; P = .14). Left ventricular chamber volume and ejection fraction did not change. CONCLUSIONS AND RELEVANCE: Transendocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction. Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00768066
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U2 - 10.1001/jama.2013.282909
DO - 10.1001/jama.2013.282909
M3 - Article
C2 - 24247587
AN - SCOPUS:84891941987
SN - 0098-7484
VL - 311
SP - 62
EP - 73
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 1
ER -