Effects of Transendocardial CD34+ Cell Transplantation on Diastolic Parameters in Patients with Nonischemic Dilated Cardiomyopathy

Abstract

We sought to evaluate the physiological background and the effects of CD34+ cell transplantation on diastolic parameters in nonischemic dilated cardiomyopathy patients (DCM). We enrolled 38 DCM patients with NYHA class III and LVEF < 40% who underwent transendocardial CD34+ cell transplantation. Peripheral blood CD34+ cells were mobilized by G‐CSF, collected via apheresis, and injected transendocardially in the areas of myocardial hibernation. Patients were followed for 1 year. At baseline, estimated filling pressures were significantly elevated (E/e′ ≥ 15) in 18 patients (Group A), and moderately elevated (E/e ′< 15) in 20 patients (Group B). The groups did not differ in age (54 ± 9 years vs. 52 ± 10 years; p = .62), gender (male: 85% vs. 78%; p = .57), or LVEF (31 ± 7% vs. 34 ± 6%; p = .37). When compared to Group B patients in Group A had more segments with myocardial scar (4.9 ± 2.7 vs. 2.7 ± 2.9; p = .03), myocardial hibernation (2.2 ± 1.6 vs. 0.9 ± 1.1; p = .02), and longer average local relaxation time on electroanatomical mapping (378 ± 41 ms vs. 333 ± 34 ms, p = .01). During follow‐up there was an improvement in diastolic parameters in Group A (E/e′: from 24.3 ± 12.1 to 16.3 ± 8.0; p = .005), but not in Group B (E/e′: from 10.2 ± 3.7 to 13.2 ± 9.1; p = .19). Accordingly, in Group A, we found an increase in 6‐minute walk distance (from 463 ± 83 m to 546 ± 91 m; p = .03), and a decrease in NT‐proBNP (from 2140 ± 1743 pg/ml to 863 ± 836 pg/ml; p = .02). In nonischemic DCM, diastolic dysfunction appears to correlate with areas of myocardial scar and hibernation. Transendocardial CD34+ cell transplantation may improve diastolic parameters in this patient cohort. Stem Cells Translational Medicine 2017;6:1515–1521

Transplantation of CD34+ cells for myocardial ischemia

“…Improvement in the 6-min walk test, left ventricular ejection fraction, N-terminal pro brain natriuretic peptide level and resting myocardial perfusion were observed after intracoronary injection of autologous CD34+ cells in patients with non-ischemic DCM and reduced ejection fraction[ 50 - 52 ]. Similar results with improvement in diastolic function were found by Bervar et al [ 53 ] after transendocardial CD34+ cell delivery in non-ischemic heart failure patients. Also, a significant decrease in the prevalence of heart failure and total mortality rate without a difference in the prevalence of sudden cardiac death were observed at 5 years after CD34+ cell transplantation therapy[ 50 ].…”

Therapeutic Potential of Endothelial Colony-Forming Cells in Ischemic Disease: Strategies to Improve their Regenerative Efficacy

“…Therefore, a number of clinical trials were conducted to assess the impact of CD34 + cell transplantation in human patients [ 83 ]. This approach did not reveal any major hurdle and proved to be safe and feasible in several ischemic disorders, including CAD [ 86 , 87 ], AMI [ 85 , 88 ], refractory angina [ 89 , 90 ], and heart failure [ 91 , 92 ]. Nevertheless, careful evaluation of the therapeutic outcome of CD34 + cell infusion provided inconsistent results, as larger randomized controlled trials failed to detect a significant improvement in coronary regrowth and myocardial angiogenesis following AMI [ 82 ].…”

Immune Dysregulation in HFpEF: A Target for Mesenchymal Stem/Stromal Cell Therapy

“…The therapeutic effect of MSC cell-based therapy on diastolic dysfunction has not been investigated. However, both CD34 + [122] and bone marrow-derived mononuclear cell (BM-MNC) therapy [118,123,124] have been associated with improved diastolic function in NIDCM and chronic ischemic cardiomyopathy, respectively. The mechanisms of action of these cell preparations are poorly understood.…”