Effects of Repetitive Transendocardial CD34⁺ Cell Transplantation in Patients With Nonischemic Dilated Cardiomyopathy.

Abstract

Preclinical data in heart failure models suggest that repetitive stem cell therapy may be superior to single-dose cell administration. We investigated whether repetitive administration of CD34⁺ cells is superior to single-dose administration in patients with nonischemic dilated cardiomyopathy. Of 66 patients with dilated cardiomyopathy, New York Heart Association 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 G-CSF (granulocyte colony-stimulating factor) 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 (N-terminal pro-B-type natriuretic peptide), 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, <i>P</i>=0.40). From baseline to 6 months, both groups improved in LVEF (+6.9±3.3% in group A, <i>P</i>=0.001 and +7.1±3.5% in group B, <i>P</i>=0.001), NT-proBNP (-578±211 pg/mL, <i>P</i>=0.02 and -633±305 pg/mL, <i>P</i>=0.01), and 6-minute walk test (+87±21 m, <i>P</i>=0.03 and +92±25 m, <i>P</i>=0.02). In contrast, we observed no significant changes between 6 months and 1 year (LVEF: +2.1±2.3% in group A, <i>P</i>=0.19 and +0.8±3.1% in group B, <i>P</i>=0.56; NT-proBNP: -215±125 pg/mL, <i>P</i>=0.26 and -33±205 pg/mL, <i>P</i>=0.77; 6-minute walk test: +27±11 m, <i>P</i>=0.2 and +12±18 m, <i>P</i>=0.42). In patients with dilated cardiomyopathy, repetitive CD34⁺ cell administration does not seem to be associated with superior improvements in LVEF, NT-proBNP, or 6-minute walk test when compared with single-dose cell therapy. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02248532.