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Published on: March 1, 2016
Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT
Alan W Heldman1, Darcy L DiFede2, Joel E Fishman3
1The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine2Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
Insights
Transendocardial stem cell injection using mesenchymal stem cells (MSCs) or bone marrow mononuclear cells (BMCs) demonstrated safety in chronic ischemic cardiomyopathy. While not definitive, results suggest potential clinical benefits warranting further investigation in larger trials.
Area of Science:
- Cardiology
- Regenerative Medicine
- Stem Cell Therapy
Background:
- Chronic ischemic cardiomyopathy leads to left ventricular dysfunction.
- The efficacy and safety of stem cell therapies, including mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (BMCs), remain under investigation.
Purpose of the Study:
- To evaluate the safety and potential efficacy of transendocardial stem cell injection using autologous MSCs and BMCs in patients with ischemic cardiomyopathy.
- To assess treatment-emergent adverse events and clinical outcomes over a 1-year follow-up period.
Main Methods:
- A phase 1/2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and ejection fraction <50%.
- Patients received injections of MSCs (n=19), BMCs (n=19), or placebo (n=21) at 10 left ventricular sites.
- Primary safety endpoint was treatment-emergent serious adverse events within 30 days; secondary endpoints included changes in heart failure scores, walk distance, infarct size, and myocardial function over 1 year.
Main Results:
- No treatment-emergent serious adverse events were observed within 30 days post-injection.
- Over 1 year, both MSCs and BMCs showed significant improvements in Minnesota Living With Heart Failure scores compared to placebo.
- MSCs, but not BMCs, significantly reduced infarct size and improved regional myocardial function; only MSCs increased 6-minute walk distance. Left ventricular ejection fraction did not change significantly in any group.
Conclusions:
- Transendocardial injection of MSCs or BMCs appears safe for patients with chronic ischemic cardiomyopathy and LV dysfunction.
- While preliminary, the study suggests potential clinical benefits of MSCs and BMCs, supporting the need for larger trials to confirm safety and efficacy.
- These findings lay the groundwork for future research into stem cell therapy for ischemic cardiomyopathy.
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, 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 Relevance:
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.
Trial Registration:
clinicaltrials.gov Identifier: NCT00768066.
