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- Title
Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial.
- Authors
Heldman, Alan W; DiFede, Darcy L; Fishman, Joel E; Zambrano, Juan P; Trachtenberg, Barry H; Karantalis, Vasileios; Mushtaq, Muzammil; Williams, Adam R; Suncion, Viky Y; McNiece, Ian K; Ghersin, Eduard; Soto, Victor; Lopera, Gustavo; Miki, Roberto; Willens, Howard; Hendel, Robert; Mitrani, Raul; Pattany, Pradip; Feigenbaum, Gary; Oskouei, Behzad
- Abstract
<bold>Importance: </bold>Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial.<bold>Objective: </bold>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.<bold>Design, Setting, and Patients: </bold>A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than 50% (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.<bold>Interventions: </bold>Injections in 10 LV sites with an infusion catheter.<bold>Main Outcomes and Measures: </bold>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.<bold>Results: </bold>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.<bold>Conclusions and Relevance: </bold>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.<bold>Trial Registration: </bold>clinicaltrials.gov Identifier: NCT00768066.
- Publication
JAMA: Journal of the American Medical Association, 2014, Vol 311, Issue 1, p62
- ISSN
0098-7484
- Publication type
journal article
- DOI
10.1001/jama.2013.282909