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 Information: www.clinicaltrials.gov; NCT02248532)
COBISS.SI-ID: 5052844
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.
COBISS.SI-ID: 4637356
Despite encouraging preclinical findings, clinical trials of repeated cell therapy are relatively scarce. As a result, the potential of this treatment paradigm remains to be assessed. We propose that a carefully planned clinicaltrial design using repeated cell dosing could lead to significant progress in the field of cell therapy.
COBISS.SI-ID: 5771692
Currently, nonischemic dilated cardiomyopathy (NICM) represents the leading cause of advanced heart failure, accounting for )50% of all heart transplantationprocedures. We propose that when compared with patients with ischemic heart failure (IHF), patients with NICM demonstrate a more favorable clinical response to cell therapy, which offers a potential novel promising treatment approch for this patient population.
COBISS.SI-ID: 4637612
We investigated a correlation between electromechanical properties of the myocardium and response to CD34+ cell therapy in patients with chronic heart failure. We enrolled 40 patients with ischemic cardiomyopathy (ICM) and 40 with nonischemic dilated cardiomyopathy (DCM). All patients were in New York Heart Association functional class III and had a left ventricular ejection fraction (LVEF) (40%. CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Electroanatomic mapping was performed to define areas of myocardial scar and hibernation, and CD34+ cells were injected transendocardially in the hibernating areas. Patients were followed for 6 months; responders were defined as patients with LVEF increase of )5%. At baseline, the groups did not differ in sex, LVEF, creatinine, N-terminal pro-B-type natriuretic peptide or electroanatomic parameters (scar area: 53?±?18% in ICM vs 55?±?23% in DCM [P?=?.83]; hibernating area: 23?±?13% vs 22?±?12% [P?=?.56]). At 6 months we found similar rates of responders in both groups (60% in ICM vs 65% in DCM [P?=?.95]). When compared with nonresponders, responders had less myocardial scar (47?±?17% vs 58?±?15% [P?=?.003]). Conclusions: In patients with chronic heart failure due to ICM and DCM we observed similar electroanatomic properties of the myocardium. In both groups, lower myocardial scar burden was associated with better clinical response to CD34+ cell therapy.
COBISS.SI-ID: 3596972