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 interventiontreated anterior ST-segment-elevation myocardial infarction and significant myocardial injury (median peak troponin I, 138 ng/mL [limits, 58-356 ng/mL]) 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, 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); it also correlated with peak TnI (r=0.76, P<0.001), severely-abnormal/absent perfusion segment number (r=0.45, P=0.008), and late gadolinium-enhanced infarct core (r=0.58, P=0.0003) 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 STsegment-elevation myocardial infarction found that myocardial cell uptake is determined by infarct size rather than LVEF and occurs preferentially in the peri-infarct zone. (Circ Cardiovasc Imaging. 2013;6:320-328.) Key Words: cardiac magnetic resonance imaging ◼ CD34 + cells ◼ gadolinium late-enhancement ◼ infarct border zone ◼ myocardial infarction-cellular therapy ◼ progenitor cell tracking ◼ single-photon emission computed tomography ◼ transcoronary cell transplantation © 2012 American Heart Association, Inc. P rogenitor cell therapy is emerging as a promising therapeutic modality in patients with acute myocardial infarction (MI) and substantial myocardial injury, and over the la...

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