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EFFICACY OF CD34+ STEM CELL THERAPY IN NON-ISCHEMIC DILATED CARDIOMYOPATHY IS ABSENT IN PATIENTS WITH DIABETES BUT PRESERVED IN PATIENTS WITH INSULIN RESISTANCE
A963 JACC March 17, 2015 Volume 65, Issue 10S
Heart Failure and Cardiomyopathies Efficacy of CD34+ Stem Cell Therapy in Non-Ischemic Dilated Cardiomyopathy Is Absent in Patients with Diabetes but Preserved in Patients with Insulin Resistance Poster Contributions Poster Hall B1 Sunday, March 15, 2015, 3:45 p.m.-4:30 p.m. Session Title: Fibrosis, Hypertrophy and Regeneration Abstract Category: 15. Heart Failure and Cardiomyopathies: Therapy Presentation Number: 1216-186 Authors: Bojan Vrtovec, Matjaz Sever, Mojca Jensterle, Gregor Poglajen, Andrej Janez, Nika Kravos, Gregor Zemljic, Marko Cukjati, Peter Cernelc, Francois Haddad, Joseph C. Wu, Ulrich P. Jorde, UMC Ljubljana, Ljubljana, Slovenia, Albert Einstein College of Medicine, New York, NY, USA Background: Diabetes has been shown to negatively affect bone marrow structure and function resulting in reduced response to mobilizing stimuli and decreased numbers of circulating CD34+ cells. We evaluated the association of diabetes and insulin resistance with CD34+ cell mobilization and clinical response to cell therapy in patients with non-ischemic dilated cardiomyopathy (DCM).
Methods: We enrolled 45 outpatients with DCM (NYHA III, LVEF<40%). All patients received granulocyte-colony stimulating factor (G-CSF; 5 mg/kg, 5 days). CD34+ cell were then collected by apheresis and injected transendocardially. Twelve patients were diabetic (DM Group), 17 had insulin resistance (IR Group), and 16 displayed normal glucose metabolism (No-IR Group). Results: After stimulation, we found significantly higher circulating numbers of CD34+ cells in IR Group (94±73x106 cells/L) than in No-IR Group (54±35x106 cells/L) or DM Group (31±20x106 cells/L, P=0.005). Consistent with this finding, apheresis yielded the highest numbers of CD34+ cell in IR group (IR Group: 216±110x106 cells; No-IR Group: 127±82x106 cells; DM Group: 77±83x106 cells, P=0.002). Six months after cell therapy we found an increase in LVEF in the IR Group (+5.6±6.9%) and the No-IR Group (+4.4±7.2%), but not in the DM Group (-0.9±5.4%, P=0.035). Furthermore, NT-proBNP levels decreased in both IR and No-IR groups, but not in the DM group (-606±850 pg/ml; -698±1105 pg/ml; +238±963 pg/ml, P=0.034). Cell therapy had the highest relative efficacy in the No-IR group (26±26x106 cells required for every 1% increase in LVEF), reduced efficacy in the IR group (75±69x106 cells required for every 1% increase in LVEF), and induced no favorable response in the DM group.
Conclusion: Transendocardial therapy with CD34+ cells appears to be ineffective in DCM patients with diabetes. Insulin resistance is associated with improved CD34+ stem cell mobilization and preserved yet less efficient clinical response to cell therapy.
Heart Failure and Cardiomyopathies Efficacy of CD34+ Stem Cell Therapy in Non-Ischemic Dilated Cardiomyopathy Is Absent in Patients with Diabetes but Preserved in Patients with Insulin Resistance Poster Contributions Poster Hall B1 Sunday, March 15, 2015, 3:45 p.m.-4:30 p.m. Session Title: Fibrosis, Hypertrophy and Regeneration Abstract Category: 15. Heart Failure and Cardiomyopathies: Therapy Presentation Number: 1216-186 Authors: Bojan Vrtovec, Matjaz Sever, Mojca Jensterle, Gregor Poglajen, Andrej Janez, Nika Kravos, Gregor Zemljic, Marko Cukjati, Peter Cernelc, Francois Haddad, Joseph C. Wu, Ulrich P. Jorde, UMC Ljubljana, Ljubljana, Slovenia, Albert Einstein College of Medicine, New York, NY, USA Background: Diabetes has been shown to negatively affect bone marrow structure and function resulting in reduced response to mobilizing stimuli and decreased numbers of circulating CD34+ cells. We evaluated the association of diabetes and insulin resistance with CD34+ cell mobilization and clinical response to cell therapy in patients with non-ischemic dilated cardiomyopathy (DCM).
Methods: We enrolled 45 outpatients with DCM (NYHA III, LVEF<40%). All patients received granulocyte-colony stimulating factor (G-CSF; 5 mg/kg, 5 days). CD34+ cell were then collected by apheresis and injected transendocardially. Twelve patients were diabetic (DM Group), 17 had insulin resistance (IR Group), and 16 displayed normal glucose metabolism (No-IR Group). Results: After stimulation, we found significantly higher circulating numbers of CD34+ cells in IR Group (94±73x106 cells/L) than in No-IR Group (54±35x106 cells/L) or DM Group (31±20x106 cells/L, P=0.005). Consistent with this finding, apheresis yielded the highest numbers of CD34+ cell in IR group (IR Group: 216±110x106 cells; No-IR Group: 127±82x106 cells; DM Group: 77±83x106 cells, P=0.002). Six months after cell therapy we found an increase in LVEF in the IR Group (+5.6±6.9%) and the No-IR Group (+4.4±7.2%), but not in the DM Group (-0.9±5.4%, P=0.035). Furthermore, NT-proBNP levels decreased in both IR and No-IR groups, but not in the DM group (-606±850 pg/ml; -698±1105 pg/ml; +238±963 pg/ml, P=0.034). Cell therapy had the highest relative efficacy in the No-IR group (26±26x106 cells required for every 1% increase in LVEF), reduced efficacy in the IR group (75±69x106 cells required for every 1% increase in LVEF), and induced no favorable response in the DM group.
Conclusion: Transendocardial therapy with CD34+ cells appears to be ineffective in DCM patients with diabetes. Insulin resistance is associated with improved CD34+ stem cell mobilization and preserved yet less efficient clinical response to cell therapy.