Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial.
BACKGROUND
Previous studies have suggested that bone marrow cell injection may improve myocardial perfusion and left ventricular (LV) function in patients with chronic myocardial ischemia.


OBJECTIVE
To investigate the effect of intramyocardial bone marrow cell injection on myocardial perfusion and LV function in patients with chronic myocardial ischemia.


METHODS
Randomized, double-blind, placebo-controlled trial at a Netherlands university hospital, May 1, 2005-March 3, 2008 (6-month follow-up ended September 2008) of 50 patients with chronic myocardial ischemia (mean age [SD], 64 [8] years; 43 men).


METHODS
severe angina pectoris despite optimal medical therapy and myocardial ischemia. All patients were ineligible for conventional revascularization.


METHODS
Intramyocardial injection of 100 x 10(6) autologous bone marrow-derived mononuclear cells or placebo solution.


METHODS
Primarily, the summed stress score, a 17-segment score for stress myocardial perfusion assessed by Tc-99m tetrofosmin single-photon emission computed tomography (SPECT). Secondary included LV ejection fraction (LVEF), Canadian Cardiovascular Society (CCS) class, and Seattle Angina Questionnaire quality-of-life score (mean difference >5% considered clinically significant).


RESULTS
After 3-month follow-up, the summed stress score (mean [SD]) improved from 23.5 (4.7) to 20.1 (4.6) (P < .001) in the bone marrow cell group, compared with a decrease from 24.8 (5.5) to 23.7 (5.4) (P = .004) in the placebo group. In the bone marrow cell-treated patients who underwent magnetic resonance imaging (MRI), a 3% absolute increase in LVEF was observed at 3 months (95% CI, 0.5% to 4.7%; n = 18), but the placebo group showed no improvement. CCS angina score improved significantly in the bone marrow cell group (6-month absolute difference, -0.79; 95% CI, -1.10 to -0.48; P < .001) compared with no significant improvement in the placebo group. Quality-of-life score increased from 56% (9%) to 64% (12%) at 3 months and 69% (12%) at 6 months in bone marrow cell-treated patients, compared with a smaller increase in the placebo group from 57% (11%) to 61% (14%) to 64% (17%). The improvements in CCS class and quality of life score were significantly greater in bone marrow cell-treated patients than in placebo-treated patients (P = .03 and P = .04, respectively).


CONCLUSIONS
In this short-term study of patients with chronic myocardial ischemia refractory to medical treatment, intramyocardial bone marrow cell injection resulted in a statistically significant but modest improvement in myocardial perfusion compared with placebo. Further studies are required to assess long-term results and efficacy for mortality and morbidity.


BACKGROUND
trialregister.nl Identifier: NTR400 and isrctn.org Identifier: ISRCTN58194927.
van Ramshorst
Jan
J
Department of Cardiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Bax
Jeroen J
JJ
Beeres
Saskia L M A
SL
Dibbets-Schneider
Petra
P
Roes
Stijntje D
SD
Stokkel
Marcel P M
MP
de Roos
Albert
A
Fibbe
Willem E
WE
Zwaginga
Jaap J
JJ
Boersma
Eric
E
Schalij
Martin J
MJ
Atsma
Douwe E
DE
D000368:Aged; D001854:Bone Marrow Cells; D017690:Cell Transplantation; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015552:Injections, Intralesional; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000628:therapy*; D055414:Myocardial Perfusion Imaging; D011788:Quality of Life; D015899:Tomography, Emission-Computed, Single-Photon; D014182:Transplantation, Autologous; D016277:Ventricular Function, Left