Abstract 18522: Higher Functional Capacity of Applied Bone Marrow-Derived Mononuclear Cells is Associated With Improved Survival of Patients With Chronic Post-Infarction Heart Failure Receiving Intracoronary Cell Therapy
The role of cell functionality to determine long-term outcome in patients undergoing cell therapy for chronic heart failure (CHF) is unknown. We evaluated whether the functional capacity of administered bone marrow-derived mononuclear cells (BM-MNC) determines clinical outcome after intracoronary administration for post-infarction CHF. During 3 years of follow-up, all-cause mortality was assessed in 297 consecutive patients (age 62±11 yrs) receiving BM-MNC for post-infarction CHF (> 3 months post AMI) between 2002 and 2008 at a single center. Colony-forming unit (CFU) capacity as a classical feature of progenitor cell function was used as a functional read-out of cell functionality. Patients were categorized into tertiles according to CFU capacity of the administered BM-MNC. Observed mortality rates were compared with the Seattle Heart Failure Model-predicted mortality, a validated multivariate mortality risk prediction model. Patients in the highest CFU-tertile had a profoundly lower observed mortality than SHFM-predicted mortality (absolute mortality risk reduction of 67.1% at 3 years), whereas no difference between observed and predicted mortality was seen in patients in the lowest tertile of CFU capacity. Accordingly, Kaplan Meier survival analysis demonstrated significantly (p<0.02) improved survival rates with increasing CFU capacity of the applied BM-MNC (see fig), which remained significant after baseline SHFM score was included into the multivariable Cox regression analysis (p<0.01). The present study for the first time discloses a dose-response relationship between applied cells and improved survival in patients with CHF. Higher clonal expansion capacity as measured by CFU of autologous BM-MNC is associated with a significant reduction in mortality after intracoronary administration in patients with CHF receiving optimal pharmacological treatment. The study is registered within www.clinicaltrials.gov (NCT00962364)
- © 2010 by American Heart Association, Inc.