Intramyocardial, autologous CD34+ cell therapy for refractory angina

Douglas W. Losordo, Timothy D. Henry, Charles Davidson, Joon Sup Lee, Marco A. Costa, Theodore Bass, Farrell Mendelsohn, F. David Fortuin, Carl J. Pepine, Jay H. Traverse, David Amrani, Bruce M. Ewenstein, Norbert Riedel, Kenneth Story, Kerry Barker, Thomas J. Povsic, Robert A. Harrington, Richard A. Schatz

Research output: Contribution to journalArticle

319 Citations (Scopus)

Abstract

Rationale: A growing number of patients with coronary disease have refractory angina. Preclinical and early-phase clinical data suggest that intramyocardial injection of autologous CD34+ cells can improve myocardial perfusion and function. Objective: Evaluate the safety and bioactivity of intramyocardial injections of autologous CD34+ cells in patients with refractory angina who have exhausted all other treatment options. Methods and Results: In this prospective, double-blind, randomized, phase II study (ClinicalTrials.gov identifier: NCT00300053), 167 patients with refractory angina received 1 of 2 doses (1×10 or 5×10 cells/kg) of mobilized autologous CD34+ cells or an equal volume of diluent (placebo). Treatment was distributed into 10 sites of ischemic, viable myocardium with a NOGA mapping injection catheter. The primary outcome measure was weekly angina frequency 6 months after treatment. Weekly angina frequency was significantly lower in the low-dose group than in placebo-treated patients at both 6 months (6.8±1.1 versus 10.9±1.2, P=0.020) and 12 months (6.3±1.2 versus 11.0±1.2, P=0.035); measurements in the high-dose group were also lower, but not significantly. Similarly, improvement in exercise tolerance was significantly greater in low-dose patients than in placebo-treated patients (6 months: 139±151 versus 69±122 seconds, P=0.014; 12 months: 140±171 versus 58±146 seconds, P=0.017) and greater, but not significantly, in the high-dose group. During cell mobilization and collection, 4.6% of patients had cardiac enzyme elevations consistent with non-ST segment elevation myocardial infarction. Mortality at 12 months was 5.4% in the placebo-treatment group with no deaths among cell-treated patients. Conclusions: Patients with refractory angina who received intramyocardial injections of autologous CD34+ cells (10 cells/kg) experienced significant improvements in angina frequency and exercise tolerance. The cell-mobilization and -collection procedures were associated with cardiac enzyme elevations, which will be addressed in future studies.

Original languageEnglish (US)
Pages (from-to)428-436
Number of pages9
JournalCirculation Research
Volume109
Issue number4
DOIs
StatePublished - Aug 5 2011

Fingerprint

Cell- and Tissue-Based Therapy
Placebos
Injections
Exercise Tolerance
Enzymes
Therapeutics
Coronary Disease
Myocardium
Cell Death
Catheters
Perfusion
Outcome Assessment (Health Care)
Safety
Mortality

Keywords

  • angiogenesis
  • endothelial progenitor cells (EPC) myocardial ischemia
  • myocardial regeneration
  • stem cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Losordo, D. W., Henry, T. D., Davidson, C., Sup Lee, J., Costa, M. A., Bass, T., ... Schatz, R. A. (2011). Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circulation Research, 109(4), 428-436. https://doi.org/10.1161/CIRCRESAHA.111.245993

Intramyocardial, autologous CD34+ cell therapy for refractory angina. / Losordo, Douglas W.; Henry, Timothy D.; Davidson, Charles; Sup Lee, Joon; Costa, Marco A.; Bass, Theodore; Mendelsohn, Farrell; Fortuin, F. David; Pepine, Carl J.; Traverse, Jay H.; Amrani, David; Ewenstein, Bruce M.; Riedel, Norbert; Story, Kenneth; Barker, Kerry; Povsic, Thomas J.; Harrington, Robert A.; Schatz, Richard A.

In: Circulation Research, Vol. 109, No. 4, 05.08.2011, p. 428-436.

Research output: Contribution to journalArticle

Losordo, DW, Henry, TD, Davidson, C, Sup Lee, J, Costa, MA, Bass, T, Mendelsohn, F, Fortuin, FD, Pepine, CJ, Traverse, JH, Amrani, D, Ewenstein, BM, Riedel, N, Story, K, Barker, K, Povsic, TJ, Harrington, RA & Schatz, RA 2011, 'Intramyocardial, autologous CD34+ cell therapy for refractory angina', Circulation Research, vol. 109, no. 4, pp. 428-436. https://doi.org/10.1161/CIRCRESAHA.111.245993
Losordo DW, Henry TD, Davidson C, Sup Lee J, Costa MA, Bass T et al. Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circulation Research. 2011 Aug 5;109(4):428-436. https://doi.org/10.1161/CIRCRESAHA.111.245993
Losordo, Douglas W. ; Henry, Timothy D. ; Davidson, Charles ; Sup Lee, Joon ; Costa, Marco A. ; Bass, Theodore ; Mendelsohn, Farrell ; Fortuin, F. David ; Pepine, Carl J. ; Traverse, Jay H. ; Amrani, David ; Ewenstein, Bruce M. ; Riedel, Norbert ; Story, Kenneth ; Barker, Kerry ; Povsic, Thomas J. ; Harrington, Robert A. ; Schatz, Richard A. / Intramyocardial, autologous CD34+ cell therapy for refractory angina. In: Circulation Research. 2011 ; Vol. 109, No. 4. pp. 428-436.
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AU - Losordo, Douglas W.

AU - Henry, Timothy D.

AU - Davidson, Charles

AU - Sup Lee, Joon

AU - Costa, Marco A.

AU - Bass, Theodore

AU - Mendelsohn, Farrell

AU - Fortuin, F. David

AU - Pepine, Carl J.

AU - Traverse, Jay H.

AU - Amrani, David

AU - Ewenstein, Bruce M.

AU - Riedel, Norbert

AU - Story, Kenneth

AU - Barker, Kerry

AU - Povsic, Thomas J.

AU - Harrington, Robert A.

AU - Schatz, Richard A.

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N2 - Rationale: A growing number of patients with coronary disease have refractory angina. Preclinical and early-phase clinical data suggest that intramyocardial injection of autologous CD34+ cells can improve myocardial perfusion and function. Objective: Evaluate the safety and bioactivity of intramyocardial injections of autologous CD34+ cells in patients with refractory angina who have exhausted all other treatment options. Methods and Results: In this prospective, double-blind, randomized, phase II study (ClinicalTrials.gov identifier: NCT00300053), 167 patients with refractory angina received 1 of 2 doses (1×10 or 5×10 cells/kg) of mobilized autologous CD34+ cells or an equal volume of diluent (placebo). Treatment was distributed into 10 sites of ischemic, viable myocardium with a NOGA mapping injection catheter. The primary outcome measure was weekly angina frequency 6 months after treatment. Weekly angina frequency was significantly lower in the low-dose group than in placebo-treated patients at both 6 months (6.8±1.1 versus 10.9±1.2, P=0.020) and 12 months (6.3±1.2 versus 11.0±1.2, P=0.035); measurements in the high-dose group were also lower, but not significantly. Similarly, improvement in exercise tolerance was significantly greater in low-dose patients than in placebo-treated patients (6 months: 139±151 versus 69±122 seconds, P=0.014; 12 months: 140±171 versus 58±146 seconds, P=0.017) and greater, but not significantly, in the high-dose group. During cell mobilization and collection, 4.6% of patients had cardiac enzyme elevations consistent with non-ST segment elevation myocardial infarction. Mortality at 12 months was 5.4% in the placebo-treatment group with no deaths among cell-treated patients. Conclusions: Patients with refractory angina who received intramyocardial injections of autologous CD34+ cells (10 cells/kg) experienced significant improvements in angina frequency and exercise tolerance. The cell-mobilization and -collection procedures were associated with cardiac enzyme elevations, which will be addressed in future studies.

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KW - angiogenesis

KW - endothelial progenitor cells (EPC) myocardial ischemia

KW - myocardial regeneration

KW - stem cells

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