Transendocardial Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells for Ischemic Cardiomyopathy: The TAC-HFT Randomized Trial
What is 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 (LV) ejection fraction <50% (September 1, 2009–July 12, 2013) was conducted. 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. Injections in 10 LV sites with an infusion catheter were administered. 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, was the main outcomes measure.
No patient had a treatment-emergent serious adverse event at day 30. The 1-year incidence of serious adverse events was 31.6 % (95% confidence interval [CI], 12.6%-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 = 0.02) and with BMCs (−8.2; 95% CI, −17.4 to 0.97; p = 0.005), but not with placebo (0.4; 95% CI, −9.45 to 10.25; p = 0.38). The 6-minute walk distance increased with MSCs only (repeated measures model, p = 0.03). Infarct size as a percentage of LV mass was reduced by MSCs (−18.9%; 95% CI, −30.4 to −7.4; within-group, p = 0.004), but not by BMCs (−7.0%; 95% CI, −15.7% to 1.7%; within-group, p = 0.11) or placebo (−5.2%; 95% CI, −16.8% to 6.5%; within-group, p = 0.36). 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 = 0.03), but not BMCs (−2.1; 95% CI, −5.5 to 1.3; p = 0.21) or placebo (−0.03; 95% CI, −1.9 to 1.9; p = 0.14). LV chamber volume and ejection fraction did not change.
The authors concluded that transendocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction.
This preliminary study reported that transendocardial stem cell injection with MSCs or BMCs appears to be safe in patients with chronic ischemic cardiomyopathy and LV dysfunction. Transendocardial injection of both cell types was not associated with an increased risk of adverse effects nor was ectopic tissue formation detected, although the small sample precludes any definitive statement about safety. Mesenchymal stem cells also exerted regenerative and antifibrotic effects within the myocardium, and these effects are associated with improved functional capacity and quality of life. Ongoing exploration of cell-based therapy for ischemic cardiomyopathy is indicated with larger studies with adequate sample size to provide definitive assessment of safety and to assess efficacy of this new therapeutic approach.
Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Implantable Devices, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Novel Agents, Acute Heart Failure, Heart Transplant
Keywords: Carbamates, Myocardial Infarction, Myocardial Ischemia, Stroke, Minnesota, Stem Cells, Heart Conduction System, Heart Transplantation, Heart Diseases, Bone Marrow, Mesenchymal Stromal Cells, Benzimidazoles, Quality of Life, Heart Failure, Hospitalization, Choristoma
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