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Objective: To investigate the association of left ventricular end-diastolic volume (LVEDV) and the response to cell therapy in patients with nonischemic dilated cardiomyopathy (NICM)., Patients and Methods: Five-year registry data from 133 consecutive patients with NICM who underwent CD34 + cell treatment were analyzed. All patients received granulocyte-colony stimulating factor; CD34 + cells were collected by apheresis and delivered by transendocardial injections. Patients with baseline LVEDV less than 200 mL (group A; n=72) and patients with LVEDV 200 to 370 mL (group B; n=54) were included. Patients with LVEDV greater than 370 mL were excluded (n=7). Favorable ejection fraction response was pre-defined by improvement in left ventricular ejection fraction (LVEF) greater than or equal to 5% at 1 y post-cell therapy., Results: At baseline, groups A and B were comparable with regards to age (52±11 y in group A vs 53±10 y in group B; P=.95), sex (male: 79% vs 83%, respectively; P=.55), creatinine (1.07±0.28 mg/dL vs 1.03±0.21 mg/dL, respectively; P=.21), or N-terminal probrain natriuretic peptide (1454±1658 pg/mL vs 1589±1338 pg/mL, respectively; P=.80). Baseline LVEF was higher in group A (32.8±8.7%) than in group B (30.2±8.7%; P=.03). During follow-up, there were four deaths in group A (5.6%), and 2 in group B (3.7%, P=.63). At 1-year post-cell therapy, LVEDV decreased significantly in group B (-56±30 mL; P=.003), but not in group A (+12±97 mL; P=.13). On multivariate analysis, baseline LVEDV was an independent correlate of favorable response in LVEF to therapy (P=.02)., Conclusion: Larger LVEDV was associated with more pronounced increase in LVEF after transendocardial CD34 + cell therapy in NICM patients, informing target individuals with the highest likelihood of regenerative response., Trial Registration: clinicaltrials.gov identifier: NCT02445534., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

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 nonischemic dilated cardiomyopathy., Methods and Results: 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, 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 6-minute walk test (+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; 6-minute walk test: +27±11 m, P =0.2 and +12±18 m, P =0.42)., Conclusions: 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., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02248532., (© 2018 American Heart Association, Inc.)

We investigated the effects of CD34 + cell therapy on right ventricular (RV) function in patients with nonischemic dilated cardiomyopathy (DCM). We enrolled 60 patients with DCM who were randomized to CD34 + cell therapy (Stem Cells (SC) Group n = 30), or no cell therapy (Controls, n = 30). The SC Group received granulocyte-colony stimulating factor, and CD34 + cells were collected by apheresis and injected transendocardially. Patients were followed for 6 months. At baseline, the groups did not differ in age, gender, left ventricular ejection fraction, N-terminal probrain natriuretic peptide, or parameters of RV function. At 6 months, we found a significant improvement in RV function in the SC Group (tricuspid annular plane systolic excursion [TAPSE]: +0.44 ± 0.64 cm, p = .001; peak systolic tissue Doppler velocity of tricuspid annulus [St]: +1.5 ± 2.1 cm/s; p = .001; percent of fractional area change [FAC]: +8.6% ± 5%, p = .01), but not in Controls (TAPSE: -0.07 ± 0.32 cm, p = .40; St: -0.1 ± 1.2 cm/s; p = .44; FAC: -1.2% ± 3.2%, p = .50). On repeat electroanatomical mapping, we found an improvement in interventricular septum viability in 19 of 30 patients from the SC Group; this correlated with the improvements in RV function (13/19 in the improved septum group versus 3/11 in the remaining cohort, p = .029). These results suggest that patients with DCM, changes in RV function correlate with changes of viability of interventricular septum. CD34 + cell therapy appears to be associated with improved right ventricular function in this patient cohort. (Clinical Trial Registration Information: www.clinicaltrials.gov; NCT02248532). Stem Cells Translational Medicine 2018;7:168-172., (© 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)