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Published on: January 24, 2014
Effects of transendocardial CD34+ cell transplantation in patients with ischemic cardiomyopathy
Gregor Poglajen1, Matjaz Sever1, Marko Cukjati1
1From the Department of Cardiology, Advanced Heart Failure and Transplantation Center (G.P., G.Z., B.V.), Department of Hematology (M.S., P.C.), and Department of Cardiovascular Surgery (I.K.), University Medical Center Ljubljana, Ljubljana, Slovenia; National Blood Transfusion Institute, Ljubljana, Slovenia (M.C.); and Stanford Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA (F.H., J.C.W., B.V.).
Insights
Transendocardial CD34(+) cell transplantation improved heart function and exercise capacity in patients with ischemic cardiomyopathy. Higher cell doses and diffuse injections yielded better results.
Area of Science:
- Cardiology
- Regenerative Medicine
- Cell Therapy
Background:
- Ischemic cardiomyopathy significantly impairs cardiac function.
- Current medical therapies have limitations in improving left ventricular ejection fraction.
- Transendocardial stem cell transplantation is an emerging therapeutic strategy.
Purpose of the Study:
- To evaluate the efficacy of transendocardial CD34(+) cell transplantation in patients with ischemic cardiomyopathy.
- To assess the impact of cell therapy on left ventricular function and exercise capacity.
Main Methods:
- Prospective crossover study involving 33 patients with NYHA class III ischemic cardiomyopathy.
- Phase 1: 6 months of medical therapy.
- Phase 2: Transendocardial injection of autologous CD34(+) cells mobilized by G-CSF, followed by 6 months of follow-up.
Main Results:
- No significant improvement in LVEF, NT-proBNP, or 6-minute walk distance during Phase 1 (medical therapy alone).
- Significant improvement in LVEF (27.1% to 34.9%, P=0.001) and 6-minute walk distance (411m to 496m, P=0.001) in Phase 2.
- Significant decrease in NT-proBNP levels (P=0.04) post-transplantation.
- Higher CD34(+) cell doses and diffuse injection patterns correlated with better clinical outcomes.
Conclusions:
- Transendocardial CD34(+) cell transplantation shows potential for improving cardiac function and exercise tolerance in ischemic cardiomyopathy.
- The benefits appear dose-dependent and related to the distribution of injected cells.
- Further research is warranted to optimize cell therapy protocols for heart failure.
Background:
We investigated the effects of transendocardial CD34(+) cell transplantation in patients with ischemic cardiomyopathy.
Methods And Results:
In a prospective crossover study, we enrolled 33 patients with ischemic cardiomyopathy with New York Heart Association class III and left ventricular ejection fraction <40%. In phase 1, patients were treated with medical therapy for 6 months. Thereafter, all patients underwent transendocardial CD34(+) cell transplantation. Peripheral blood CD34(+) cells were mobilized by granulocyte colony stimulating factor, collected via apheresis, and injected transendocardially in the areas of hibernating myocardium. Patients were followed up for 6 months after the procedure (phase 2). Two patients died during phase 1 and none during phase 2. The remaining 31 patients were 85% men, aged 57±6 years. In phase 1, we found no change in left ventricular ejection fraction (from 25.2±6.2% to 27.1±6.6%; P=0.23), N-terminal pro B-type natriuretic peptide (from 3322±3411 to 3672±5165 pg/mL; P=0.75) or 6-minute walk distance (from 373±68 to 411±116 m; P=0.17). In contrast, in phase 2 there was an improvement in left ventricular ejection fraction (from 27.1±6.6% to 34.9±10.9%; P=0.001), increase in 6-minute walk distance (from 411±116 to 496±113 m; P=0.001), and a decrease in N-terminal pro B-type natriuretic peptide (from 3672±5165 to 1488±1847 pg/mL; P=0.04). The average number of injected CD34(+) cells was 90.6±7.5×10(6). Higher doses of CD34(+) cells and a more diffuse distribution of transendocardial cell injections were associated with better clinical response.
Conclusions:
Transendocardial CD34(+) cell transplantation may be associated with improved left ventricular function, decreased N-terminal pro B-type natriuretic peptide levels, and better exercise capacity in patients with ischemic cardiomyopathy. These effects seem to be particularly pronounced in patients receiving diffusely distributed cell injections and high-dose cell therapy.
Clinical Trial Registration Url:
http://www.clinicaltrials.gov. Unique identifier: NCT01350310.
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