Abstract

Rationale: Preclinical data in heart failure models suggest that repetitive stem cell therapy may be superior to single-dose cell administration. Objective: We investigated whether repetitive administration of CD34+ cells is superior to single dose administration in patients with non-ischemic dilated cardiomyopathy (DCM). Methods and Results: Of 66 patients with DCM, NYHA functional class III, and left ventricular ejection fraction (LVEF)< 40% enrolled in the study, 60 were randomly allocated to repetitive cell therapy (Group A, N=30), or single cell therapy (Group B, N=30). Patients received granulocyte-colony stimulating factor (G-CSF) for 5 days and 80 million CD34+ cells were collected by apheresis and injected transendocardially. In Group A, cell therapy was repeated at 6 months. All patients were followed for 1 year, and the primary end-point was the difference in change in LVEF between the groups. At baseline, the groups did not differ in age, sex, LVEF, NT-proBNP, or 6-minute walk test distance. When directly comparing groups A and B at 1 year, there was no significant difference in change in LVEF (from 32.2±9.3% to 41.2±6.5% in Group A and from 30.0±7.0% to 37.9±5.3% in Group B, P=0.40). From baseline to 6 months, both groups improved in LVEF (+6.9±3.3% in Group A, P=0.001 and +7.1±3.5% in Group B, P=0.001), NT-proBNP (-578±211 pg/ml, P=0.02 and -633±305 pg/ml, P=0.01) and 6MWT (+87±21 m, P=0.03 and +92±25 m, P=0.02). In contrast, we observed no significant changes between 6 months and 1 year (LVEF: +2.1±2.3% in Group A, P=0.19 and +0.8±3.1% in Group B, P=0.56; NT-proBNP: -215±125 pg/ml, P=0.26 and -33±205 pg/ml, P=0.77; 6MWT: +27±11 m, P=0.2 and +12±18 m, P=0.42). Conclusions: In patients with DCM, repetitive CD34+ cell administration does not appear to be associated with superior improvements in LVEF, NT-proBNP, or 6MWT when compared to single dose cell therapy. Clinical Trial: NCT02248532.

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