Abstract 15453: CD34+ Cell Therapy May Affect Extracellular Matrix Turnover in Patients With Non-ischemic Dilated Cardiomyopathy

Abstract

Introduction: The underlying mechanisms of CD34+ cell therapy in patients with non-ischemic dilated cardiomyopathy (DCM) remain poorly defined Hypothesis: We sought to evaluate the effects of CD34+ cell therapy on extracellular matrix. Methods: We performed a cohort analysis of 23 consecutive patients with DCM who underwent transendocardial CD34+ cell transplantation between January and December 2013. All patients received 5-day stimulation with G-CSF; CD34+ cells were selected with apheresis and injected transendocardially guided by electroantomical mapping. Patients were followed for 6 months and good clinical response was defined as an increase of left ventricular ejection fraction (LVEF) ≥5%. Extracellular matrix turnover was evaluated by measuring changes in galectin-3 serum levels. Results: Within 6 months after cell therapy galectin-3 levels decreased in 9 (39%) patients (Group A) and increased in 14 (61%, Group B). The two groups did not differ with regards to gender (male: 100% in Group A vs. 78% in Group B; P=0.15), age (51±10 years vs. 52±11 years; P=0.79), serum creatinine (86±22 μmol/L vs. 82±17 μmol/L, P=0.62), bilirubine (20±11 μmol/L vs. 17±9 μmol/L, P=0.51), or NT-proBNP levels (1465±1448 pg/mL vs. 1380±1626 pg/mL, P=0.72). Baseline LVEF (28±9% vs. 33±7%, P=0.10) and left ventricular end-diastolic diameter (7.1±0.8 cm vs. 6.5±0.7 cm, P=0.22) were also comparable in the two groups. Both groups received comparable doses of CD34+ cells (84±51 million cells in Group A vs. 132±96 million cells in Group B, P=0.21). At 6 months LVEF increased significantly more in Group A than in Group B (9.2±5.1% vs. 3.4±5.2%, P=0.01) and the same was true for 6-minute walk test distance (83±47 m vs. 37±27 m, P=0.03). NT-proBNP decreased in Group A (-356±684 pg/mL), but not in Group B (+449±1040 pg/mL, P=0.07) and overall clinical response was significantly better in Group A than in Group B (responders: 88% vs. 33%, P=0.008). Conclusions: In non-ischemic DCM, clinical response to CD34+ cell therapy appears to correlate with changes in galectin-3 serum levels. This suggests that the effects of CD34+ cell therapy may be partially mediated through remodelling of the extracellular matrix.