Infarct Size Determines Myocardial Uptake of CD34 + Cells in the Peri-Infarct Zone

Abstract

Background— Effective progenitor cell recruitment to the ischemic injury zone is a prerequisite for any potential therapeutic effect. Cell uptake determinants in humans with recent myocardial infarction are not defined. We tested the hypothesis that myocardial uptake of autologous CD34 + cells delivered via an intracoronary route after recent myocardial infarction is related to left ventricular (LV) ejection fraction (LVEF) and infarct size. Methods and Results— Thirty-one subjects (age, 36–69 years; 28 men) with primary percutaneous coronary intervention–treated anterior ST-segment–elevation myocardial infarction and significant myocardial injury (median peak troponin I, 138 ng/dL [limits, 58–356 ng/dL]) and sustained LVEF depression at ≤45% were recruited. On day 10 (days 7–12), 4.3×10 6 (0.7–9.9×10 6 ) 99m Tc-extametazime–labeled autologous bone marrow CD34 + cells (activity, 77 MBq [45.9–86.7 MBq]) were administered transcoronarily (left anterior descending coronary artery). 99m Tc-methoxyisobutyl isonitrile (99 m Tc-MIBI) single-photon emission computed tomography before cell delivery showed 7 (2–11) (of 17) segments with definitely abnormal/absent perfusion. Late gadolinium-enhanced infarct core mass was 21.7 g (4.4–45.9 g), and infarct border zone mass was 29.8 g (3.9–60.2 g) (full-width at half-maximum, signal intensity thresholding algorithm). One hour after administration, 5.2% (1.7%–9.9%) of labeled cell activity localized in the myocardium (whole-body planar γ scan). Image fusion of labeled cell single-photon emission computed tomography with LV perfusion single-photon emission computed tomography or with cardiac magnetic resonance infarct imaging indicated cell uptake in the peri-infarct zone. Myocardial uptake of labeled cells activity correlated in particular with late gadolinium-enhanced infarct border zone mass ( r =0.84, P <0.0001) and with peak troponin I ( r =0.76, P <0.001); it also correlated with severely abnormal/absent perfusion segment number ( r =0.45, P =0.008) and late gadolinium-enhanced infarct core ( r =0.58 and r =0.84, P <0.0001) but not with echocardiography LVEF ( r =−0.07, P =0.68) or gated single-photon emission computed tomography LVEF ( r =−0.28, P =0.16). The correlation with cardiac magnetic resonance imaging-LVEF was weak ( r =−0.38; P =0.04). Conclusions— This largest human study with labeled bone marrow CD34 + cell transcoronary transplantation after recent ST-segment–elevation myocardial infarction found that myocardial cell uptake is determined by infarct size rather than LVEF and occurs preferentially in the peri-infarct zone.