Effect of Progenitor Cells on Myocardial Perfusion and Metabolism in Patients After Recanalization of a Chronically Occluded Coronary Artery

Abstract

Even after recanalization of a chronic total coronary occlusion, functional recovery is incomplete and parts of the myocardium remain hypoperfused. In this randomized, placebo-controlled, and double-blinded study, we investigated relative changes in myocardial perfusion and glucose metabolism induced by intracoronary administration of blood-derived circulating progenitor cells (CPCs), compared with the natural course in a control group after recanalization of total coronary occlusion. Methods: After recanalization of total coronary occlusion, 26 patients were randomly assigned to the CPC treatment or placebo group. Regional myocardial perfusion and glucose metabolism were assessed by 99m Tc-tetrofosmin SPECT and 18 F-FDG PET at baseline (after recanalization of total coronary occlusion) and 3 mo after the administration of 69 6 14 · 10 6 CPCs or cell-free serum, respectively. Segments were classified as ''normal,'' ''perfusion-metabolism mismatch'' (dysfunctional segments with a 99m Tc-tetrofosmin-18 F-FDG mismatch), or ''scar.'' Results: In contrast to the placebo group, CPC administration resulted in a significant decrease in the number of segments with a perfusionmetabolism mismatch, from 3.0 6 0.5 to 1.7 6 0.6 segments (P , 0.05 vs. baseline). Of the normal segments at baseline, 2.7% in the CPC group and 30% in the placebo group revealed a perfusionmetabolism mismatch at follow-up after 3 mo (P , 0.05 vs. placebo). Conclusion: Intracoronary administration of CPCs significantly reduces the amount of myocardium with a perfusionmetabolism mismatch and prevents areas with normal perfusion and metabolism after recanalization of total coronary occlusion from becoming dysfunctional during the next 3 mo. These results show that PET and SPECT can be used to monitor the effect of progenitor cells on myocardial integrity. More important, they provide evidence supporting expansion of the use of progenitor cell treatment to chronic coronary artery disease. Pat ients with total occlusion of a main coronary artery are known to benefit significantly from recanalization with regard to major cardiac events (1), long-term survival (2), improvement of left ventricular function (3), and myocardial flow reserve (4). Nevertheless, functional recovery is incomplete, and parts of the myocardium remain with a perfusionmetabolism mismatch (5-7). However, the underlying mechanisms are not fully understood (7). One speculation is that parts of the myocardium are insufficiently supplied because of persistent paradoxical vasoconstriction of epicardial vessels and microvascular dysfunction (8).Lately, experimental and clinical studies using progenitor cells have shown functional recovery and improved myocardial perfusion in chronic myocardial ischemia (9,10). To investigate whether progenitor cells also demonstrate such a benefit after recanalization of total coronary occlusion, we conducted a randomized, placebo-controlled, and doubleblinded study with intracoronary administration of bloodderived circulating progenitor cells (CPCs) in pat...

SPECT and PET to optimize cardiac stem cell therapy

“…Hence, it is important to quantify engraftment in vivo and examine the influence of cell number on functional benefit and cardiac electrophysiology. PET and SPECT imaging have the potential to play a major role in pre-clinical and clinical studies of stem cell therapies because they provide information on myocardial viability, ejection fraction, infarct size, coronary flow reserve, and myocardial perfusion (which are important endpoints following stem cell transplantation) [1][2][3]6,7,9,[12][13][14]16,19,[21][22][23][24][27][28][29][35][36][37][38][39][40][41][42][43] in addition to permitting quantification of stem cell engraftment.…”

Cardiac Repair with Adult Bone Marrow-Derived Cells: The Clinical Evidence

“…Consistent with this notion, in the TOPCARE-CHD trial, BMMNC therapy but not CPC therapy was able to improve outcome variables in patients with chronic IHD (7). In contrast, in the study by Erbs et al (24,45), CPC injection was effective in improving both global and regional wall motion in patients with chronic total occlusion. Importantly, compared with the TOPCARE-CHD study (7), Erbs et al (24) injected nearly threefold greater number of CPCs (22 AE 11 vs. 69 AE 14 million) within a shorter time window following MI (77 AE 76 vs. 7.5 AE 2.9 months).…”

“…In contrast, in an earlier RCT by Erbs et al (24), intracoronary CPC injection in patients with IHD and chronic total occlusion of coronary artery reduced infarct size, improved regional wall motion and global LVEF, decreased the number of hibernating myocardial segments, and increased coronary flow reserve. These results (24) suggest that the benefits of late reperfusion may be enhanced by concomitant CPC therapy, which improves myocardial perfusion=metabolism mismatch in these patients (45). However, the role of myocardial milieu (acutely infarcted versus remodeled myocardium) as a determinant of outcomes following CPC transplantation needs to be examined in future clinical trials.…”

Clinical Trials of Cardiac Repair with Adult Bone Marrow- Derived Cells

“…As an example of this cell-specific efficacy, BMMNCs but not CPCs were able to improve outcomes in patients with chronic cardiomyopathy in the TOPCARE-CHD trial [30]. However, CPC injection improved global LV function and regional wall motion in patients with chronic total occlusion in the study by Erbs et al [65, 90]. Importantly, Erbs et al injected larger number of CPCs (69 ± 14 million vs. 22 ± 11 million) at a shorter time interval after MI (7.5 ± 2.9 months vs. 77 ± 76 months) compared with the TOPCARE-CHD study [30], [65].…”