Abstract 16663: Patient and Cell Characteristics Associated With Clinical Outcomes in the CCTRN LateTIME Trial

Abstract

Background and Hypothesis: In the CCTRN LateTIME trial, there was no improvement versus placebo in cardiac function 6 months after intracoronary infusion of autologous bone marrow mononuclear cells (BMC), 2-3 weeks post-MI. We hypothesized that clinical outcomes are associated with patient demographics and BMC populations that contribute to the efficacy of the intervention. Methods: Left ventricular (LV) function was evaluated at baseline and at 6 months. BMC study product data associated with phenotype and colony formation capability were collected at baseline. Principal components analysis was used to define a composite variable, LV dysfunction, encompassing both LV volume and wall motion data. Case control analysis was then conducted comparing those with improved LV dysfunction (cases) with those without (controls). Results: Hypertension, diabetes, and obesity were associated with lower levels of endothelial progenitor cells; whereas hyperlipidemia was inversely associated with CD11b+ cells, and obesity with CD3+ cells. Adjusted multivariate analysis indicated that CD11b+ cells were negatively associated with LV function; both globally (P<0.02) and regionally (P<0.01 and P<0.001, border and infarct zone wall motion, respectively). Global LV function was positively associated with MSC colonies formed (P<0.02) and regional LV function (border zone wall motion) and with cell viability (P<0.03). Case control analysis revealed a significant association of CD133+, CD34+/CD31+, and CXCR4dim cells with cases. Increased LV dysfunction was associated with CD11b+cells. Conclusions: These results suggest that CVD risk factors significantly affect BMC and that baseline BMC characteristics of individual patients may be important determinants of clinical improvement. Higher frequencies or better function of specific cell populations with endothelial, mesenchymal and migratory phenotype may predispose patients to clinical improvements, whereas higher level of CD11b+ in the BM may contribute to impaired LV function. Product selection or treatment to modify bone marrow constituents, such as negative selection of CD11b+ cells prior to BMC injection, may be a potential strategy to improve outcomes of future clinical trials.