Individual differences in the effectiveness of intracoronary bone marrow cell transplantation assessed by gated sestamibi SPECT/FDG PET imaging.

BACKGROUND: The impact of different levels of tracer uptake on improvements of left-ventricular (LV) function was analyzed in patients treated by intracoronary bone marrow cell (BMC) transplantation. METHODS AND RESULTS: Thirty-one patients with irreversible damage after their first acute myocardial infarction (MI), as confirmed by sestamibi single-photon emission computed tomography (MIBI SPECT)/fluorodeoxyglucose positron emission tomography (FDG PET), underwent high-dose (1 x 10(8) cells) BMC transplantation, whereas 31 similar patients were randomly integrated into a control group. In 11 BMC-treated patients with very low sestamibi uptake at less than 30% of maximum in the infarcted area, the mean left-ventricular ejection fraction (LVEF) improved after 3 months of follow-up by 3% only, and mean end-diastolic/end-systolic volumes (EDV/ESV) enlarged by 10/1 mL (P = NS vs controls). In 20 BMC-treated patients with higher sestamibi uptake in the range of 31% to 50% of maximum, LVEF improved by 7%, and EDV/ESV decreased by 5/12 mL (P < .05 vs BMC-treated subgroup with low MIBI uptake and controls). No similar categorization was seen in the control group: in patients with higher sestamibi uptake or very low uptake, the LVEF increased by 2% and 3% only, and the EDV/ESV enlarged in both subgroups by 12/4 mL and 12/2 mL, respectively (P = NS). CONCLUSIONS: Our results suggest the capability of SPECT/PET imaging to select patients who will receive the maximum benefit from BMC therapy.

Cell therapy in patients with left ventricular dysfunction due to myocardial infarction.

OBJECTIVES: The purpose of this study was to determine the impact of autologous transplantation of mononuclear bone marrow cells on myocardial function in patients with left ventricular (LV) dysfunction due to an acute myocardial infarction. METHODS: The randomized study included 82 patients with a first acute myocardial infarction treated with a stent implantation. This presentation is a subanalysis of 47 patients with left ventricular dysfunction-EF (ejection fraction)

Three-, 6-, and 12-month results of autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction.

BACKGROUND: There are only few data on long-term effectiveness of the stem cell therapy. AIM: We studied the time course of global and regional left ventricular function in patients with acute myocardial infarction within 1 year after the autologous mononuclear bone marrow cell transplantation. METHODS: Sixty patients with a first acute myocardial infarction, who had been randomized into 3 groups, completed a 12-month protocol. Two groups were intracoronarily given bone marrow cells in either higher (10(8) cells, HD group, n=20) or lower (10(7) cells, LD group, n=20) doses. Twenty patients without cell transplantation served as a control (C) group. Doppler tissue imaging and the gated technetium-99m sestamibi single photon emission computed tomography were performed before cell transplantation and at 3, 6, and 12 months later. RESULTS: The baseline peak systolic velocities of longitudinal contraction of the infarcted wall (S(infarct)) of 5.2 cm/s, 4.6 cm/s, and 4.4 cm/s in C, LD, and HD groups increased by 0.0 cm/s, 0.3 cm/s (p=NS vs. C group), and by 0.7 cm/s (p<0.05 vs. C group), respectively, at 3 months. At 12 months, however, the corresponding changes from baseline values of 0.1 cm/s, 0.2 cm/s, and 0.6 cm/s did not differ significantly (all p=NS). In contrast, the post-transplant improvements in the left ventricular ejection fraction by 6%, 7%, and 7% at months 3, 6, and 12, respectively, were preserved in HD group patients during the whole 12-month follow-up and remained significantly better as compared to controls. CONCLUSIONS: In our study, the autologous mononuclear bone marrow cell transplantation provided sustained improvement in global left ventricular systolic function in patients with acute myocardial infarction. However, when evaluating regional systolic function of the infarcted wall, the short-term benefit was partially lost during the 12-month follow-up.

Autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction: the effect of the dose of transplanted cells on myocardial function.

BACKGROUND: Despite the reports on successful treatment of acute myocardial infarction using autologous mononuclear bone marrow cell transplantation, many unresolved questions still remain. We studied the impact of the dose of transplanted cells on myocardial function and perfusion. METHODS: Sixty-six patients with a first acute myocardial infarction were randomized into 3 groups. Two groups were intracoronarily given mononuclear bone marrow cells in either higher (10(8) cells, higher cell dose [HD] group, n = 22) or lower (10(7) cells, lower cell dose [LD] group, n = 22) doses. Twenty-two patients without cell transplantation served as a control (C) group. RESULTS: At 3 months of follow-up, the baseline peak systolic velocities of longitudinal contraction of the infarcted wall of 5.2, 4.5, and 4.3 cm/s in C, LD, and HD groups increased by 0.0, 0.5 (P < .05 vs C group), and 0.9 cm/s (P < .05 vs LD group, P < .01 vs C group), respectively, as demonstrated by Doppler tissue imaging. Baseline left ventricular ejection fractions of 42%, 42%, and 41% in C, LD, and HD groups increased by 2%, 3%, and by 5% (P < .05 vs group C), respectively, as assessed by the gated technetium Tc 99m sestamibi single photon emission computed tomography. CONCLUSIONS: Mononuclear bone marrow cell transplantation improves regional myocardial function of the infarcted wall in a dose-dependent manner.

The role of quantitative Tc-99m-MIBI gated SPECT/F-18-FDG PET imaging in the monitoring of intracoronary bone marrow cell transplantation.

BACKGROUND: A lot of unresolved questions still exist concerning the exact mechanism of the beneficial effects of bone marrow cell (BMC) transplantation for myocardial regeneration. The aim of this communication is to report the cases of patients with and without post-transplantation left ventricular function improvement. MATERIAL AND METHODS: To this study we included consecutive patients with irreversible damage after a first acute ST-elevation myocardial infarction treated by coronary angioplasty with stent implantation. The irreversible damage was identified by dobutamine echocardiography and confirmed by rest gated Tc-99m-MIBI gated SPECT and in the majority of patients by F-18-FDG PET imaging as well. Using 4D-MSPECT software, we quantified MIBI/FDG uptake and gated SPECT left ventricular ejection fraction, end-diastolic/end-systolic volumes (LVEF, EDV/ESV) before BMC therapy and 3 months later. RESULTS: The results obtained in the initial group of patients in this study (27 patients in the BMC treated group, 16 patients in the control group) have been published previously [Eur J Nucl Med 2005; 32 (Suppl 1 ): S46]. Among the BMC group, we identified 13 responders to therapy with average LVEF improvement from 43.3% +/- 11% to 51.4% +/- 10.4% and EDV/ESV improvement from 145 ml/84 ml to 133 ml/67 ml. The remaining 14 patients were non-responders to therapy with no significant change in LVEF (39.1% +/- 8.1% versus 39.8% +/- 7.4%), the EDV/ESV increased from 166 ml/105 ml to 188 ml/116 ml. Responders to the cell therapy had prevailing MIBI uptake in the range of 31-50% of maximum in the infarction territory. On the other hand, non-responders to BMC therapy had prevailing MIBI uptake in the range of 0-30% of maximum. Two cases are presented in this report. CONCLUSIONS: Further studies with a larger cohort of patients would be helpful to evaluate our findings. We observed strong interindividual differences in the effectiveness of the cell therapy. Prevailing residual MIBI uptake in the range of 31-50% of maximum was in the subgroup of responders to the cell therapy.