Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial.
The aim of TAC-HFT trial was 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.
A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular ejection fraction less than 50% ( 2009-2013 ) was performed.
The study has compared injection of MSCs ( n=19 ) with placebo ( n = 11 ) and BMCs ( n = 19 ) with placebo ( n = 10 ), with 1 year of follow-up.
Main endpoint was 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.
No patient had a treatment-emergent serious adverse events at day 30. The 1-year incidence of serious adverse events was 31.6% for MSCs, 31.6% for BMCs, and 38.1% for placebo.
Over 1 year, the Minnesota Living With Heart Failure score improved with MSCs ( −6.3; repeated measures of variance, P=0.02 ) and with BMCs ( −8.2; P=0.005 ) but not with placebo ( 0.4; P=0.38 ).
The 6-minute walk distance increased with MSCs only ( repeated measures model, P = 0.03 ).
Infarct size as a percentage of left ventricular mass was reduced by MSCs ( −18.9%; within-group, P =0 .004 ) but not by BMCs ( −7.0%; within-group, P = 0.11 ) or placebo ( −5.2%; within-group, P =0 .36 ).
Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs ( −4.9; within-group repeated measures, P =0 .03 ) but not BMCs ( −2.1; P = 0.21 ) or placebo ( −0.03; P = 0.14 ).
Left ventricular chamber volume and ejection fraction did not change.
In conclusion, transendocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and left ventricular 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. ( Xagena )
Heldman AW et al, JAMA 2014;311:62-73