Abstract 16945: Identification of Peripheral Blood Mononuclear Cell Subpopulations in Chronic Left Ventricular Dysfunction Patients With Improved Functional Outcomes: A Biorepository Evaluation From the CCTRN FOCUS Trial

Background: Although cell therapy could potentially slow or reverse progression of chronic ischemic heart failure (HF), clinical trials of bone marrow-derived mononuclear cells (BM-MNC) have met with minimal success. It is unknown why some patients improve (i.e. improvers) and others do not (i.e. non-improvers). B cell numbers, in fact, have been associated with improvement after acute myocardial infarction (MI). We hypothesized that improvers have a higher percentage of B cells in peripheral blood (PB) vs. non-improvers after study treatment. Methods: We used flow cytometry to evaluate temporal changes in the frequency of PB subpopulations after BM-MNC or placebo therapy in HF patients enrolled in the FOCUS-CCTRN trial. PB was collected at day 0 (baseline) and days 1, 30, 90, and 180 from consented participants. Cohort 1 (n=17) patients, who improved in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (ESV), and maximal oxygen consumption (VO 2 max) during the 6-month course, were compared to patients who declined in the above three outcomes, cohort 2 (n=11). Linear mixed model was used to determine the changes over time in each cell population. The difference between each time point to day 0 was calculated as linear contrast. Results: Cohort 1 had a higher frequency of B cells (CD45+CD19+) at day 0 (15.24±7.55 vs. 8.95±3.49, p=0.002), day 1 (14.67±5.53 vs. 8.78±4.51, p=0.003), day 90 (14.98±6.64 vs. 8.49±4.33, p=0.006) and day 180 (13.44±7.85 vs. 8.07±4.34, p=0.033) and regulatory B cells (CD19+CD11B+) at day 0 (2.06±1.20 vs. 1.09±0.58, p=0.011) and day 90 (2.49±1.50 vs. 1.32±0.62, p=0.016) when compared to cohort 2. Both cohorts had an increase in CD11B+ at day 1 when compared to baseline (91.53±3.43 vs. 93.09±3.69, p=0.020) (92.01±3.63 vs. 94.60±8.70, p=0.005), which remained higher in cohort 2 until day 30 (92.01±3.63 vs. 93.92±1.91, p=0.020). Conclusion: A higher frequency of B cells and subsets was observed in PB of patients who improved independent of treatment. These data support prior findings of the importance of B cells in recovery after MI and suggest an important relationship between the humoral immune system and HF.