Effect of intramyocardial injection of autologous bone marrow-derived mononuclear cells on perfusion, function, and viability in patients with drug-refractory chronic ischemia.
Intramyocardial injection of bone marrow cells has been proposed as a new therapeutic option for patients with chronic ischemic heart disease. We investigated whether autologous bone marrow-derived mononuclear cell injection into the myocardium of patients with drug-refractory ischemia reduces anginal symptoms, improves left ventricular (LV) function, increases myocardial perfusion, and alters the extent of scar tissue.


METHODS
In 25 patients (mean age +/- SD, 64 +/- 10 y; 21 male) with drug-refractory angina pectoris (Canadian Cardiovascular Society [CCS] class III-IV), despite optimized medical therapy and without options for conventional revascularization, bone marrow was aspirated from the iliac crest. Mononuclear cell injections were targeted at myocardial regions with stress-induced ischemia on gated (99m)Tc-tetrofosmin SPECT. Anginal symptoms were reassessed at 3- and 6-mo follow-up. At baseline and 3-mo follow-up, gated (99m)Tc-tetrofosmin SPECT and (18)F-FDG SPECT were performed to assess LV function, LV volumes, myocardial perfusion (stress and rest, 17-segment model), and extent of scar tissue.


RESULTS
Mean CCS score improved from 3.4 +/- 0.6 at baseline to 2.3 +/- 0.6 at 3 mo (P < 0.01) and remained unchanged at 6 mo (2.3 +/- 0.6; P < 0.01 vs. baseline and P = not significant [NS] vs. 3 mo). Gated (99m)Tc-tetrofosmin SPECT demonstrated an increased LV ejection fraction (from 47.6% +/- 13.5% to 54.1% +/- 16.9%; P < 0.01) and a reduced LV end-systolic volume (from 81 +/- 68 mL to 75 +/- 70 mL; P < 0.01). Segmental regional wall thickening increased from 34% +/- 12% at baseline to 39% +/- 17% at 3-mo follow-up (P = 0.01). The number of segments with stress-inducible ischemia per patient decreased from 4.6 +/- 3.2 to 2.0 +/- 2.6 (P < 0.01). Both segmental stress and segmental rest score improved, although the improvement in stress score was more pronounced (decrease in segmental stress score 0.22 +/- 0.20 vs. decrease in segmental rest score 0.04 +/- 0.06; P < 0.01). Myocardial perfusion improved in 53% of the injected segments and in 13% of the noninjected segments (P < 0.01). The percentage of myocardial segments with some extent of scar remained unchanged at 3-mo follow-up (13% vs. 12%; P = NS).


CONCLUSIONS
Autologous bone marrow-derived mononuclear cell injection in patients with drug-refractory angina and chronic ischemia improves anginal symptoms, increases LV function, and predominantly enhances myocardial stress perfusion in injected segments, whereas the extent of myocardial scar tissue remains unchanged.
Beeres
Saskia L M A
SL
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Bax
Jeroen J
JJ
Dibbets
Petra
P
Stokkel
Marcel P M
MP
Zeppenfeld
Katja
K
Fibbe
Willem E
WE
van der Wall
Ernst E
EE
Schalij
Martin J
MJ
Atsma
Douwe E
DE
D000368:Aged; D000787:Angina Pectoris / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy; D016026:Bone Marrow Transplantation; D002908:Chronic Disease; D004351:Drug Resistance; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007267:Injections; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D015425:Myocardial Reperfusion; D009206:Myocardium; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon; D014182:Transplantation, Autologous; D016277:Ventricular Function, Left
D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C078700:technetium tc-99m tetrofosmin