title: Effect of intramyocardial injection of autologous bone marrow-derived mononuclear cells on perfusion, function, and viability in patients with drug-refractory chronic ischemia.
abstract: 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.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Saskia L M A
authors.initials: SL
authors.lastname: Beeres
authors.forename: Jeroen J
authors.initials: JJ
authors.lastname: Bax
authors.forename: Petra
authors.initials: P
authors.lastname: Dibbets
authors.forename: Marcel P M
authors.initials: MP
authors.lastname: Stokkel
authors.forename: Katja
authors.initials: K
authors.lastname: Zeppenfeld
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: Ernst E
authors.initials: EE
authors.lastname: van der Wall
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schalij
authors.forename: Douwe E
authors.initials: DE
authors.lastname: Atsma
mesh_terms: 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
chemical_list: D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C078700:technetium tc-99m tetrofosmin