Transendocardial Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells for Ischemic Cardiomyopathy: The TAC-HFT Randomized Trial
01/2014
Journal Article
Authors:
Heldman, A.W.;
DiFede, D.L.;
Fishman, J.E.;
Zambrano, J.P.;
Trachtenberg, B.H.;
Karantalis, V.;
Mushtaq, M.;
Williams, A.R.;
Suncion, V.Y.;
McNiece, I.K.;
Ghersin, E.;
Soto, V.;
, ;
Da Silva, J.;
Anderson, E.;
Schwarz, R.;
Mendizabal, A.;
Hare, J.M.
Secondary:
JAMA
Volume:
311
Pagination:
62-73
URL:
http://www.ncbi.nlm.nih.gov/pubmed/24247587
Keywords:
Aged; Bone Marrow Transplantation; Cardiomyopathies; Disease Progression; Double-Blind Method; Mesenchymal Stem Cell Transplantation; myocardial infarction; Stroke; Survival Analysis; Transplantation-Autologous; Treatment Outcome; Ventricular Dysfunction
Abstract:
{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 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. 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
