• Alan W Heldman, Darcy L DiFede, Joel E Fishman, Juan P Zambrano, Barry H Trachtenberg, Vasileios Karantalis, Muzammil Mushtaq, Adam R Williams, Viky Y Suncion, Ian K McNiece, Eduard Ghersin, Victor Soto, Gustavo Lopera, Roberto Miki, Howard Willens, Robert Hendel, Raul Mitrani, Pradip Pattany, Gary Feigenbaum, Behzad Oskouei, John Byrnes, Maureen H Lowery, Julio Sierra, Mariesty V Pujol, Cindy Delgado, Phillip J Gonzalez, Jose E Rodriguez, Luiza Lima Bagno, Didier Rouy, Peter Altman, Cheryl Wong Po Foo, Jose da Silva, Erica Anderson, Richard Schwarz, Adam Mendizabal, and Joshua M Hare.
• The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
• JAMA. 2014 Jan 1;311(1):62-73.

ImportanceWhether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial.ObjectiveTo 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 PatientsA 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.InterventionsInjections in 10 LV sites with an infusion catheter.Main Outcomes And MeasuresTreatment-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.ResultsNo 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 RelevanceTransendocardial 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 Registrationclinicaltrials.gov Identifier: NCT00768066.

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