Abstract
Cell therapy trials for heart failure (HF) have shown modest improvement; however, the mechanisms underlying improvement in some patients but not others are not well understood. Although immune cells are important in the course of HF, our understanding of the immune processes in HF is limited. The objective of this study was to evaluate associations between temporal changes in peripheral blood (PB) cell subpopulations and improved outcome in patients with chronic ischemic cardiomyopathy after bone marrow-derived mononuclear cell therapy or placebo in the FOCUS-CCTRN trial. Peripheral blood was collected at days 0, 1, 30, 90, and 180 from consented participants. We used flow cytometry to compare PB populations in patients with the best (cohort 1) or worst functional outcome (cohort 2) in three primary endpoints: left ventricular (LV) ejection fraction, LV end-systolic volume, and maximal oxygen consumption (VO2 max). A linear mixed model was used to assess changes over time in 32 cell populations. The difference between each time point and baseline was calculated as linear contrast. Compared with cohort 2, patients who improved (cohort 1) had a higher frequency of CD45+CD19+ B cells at days 0, 1, 90, and 180. CD11B+ cells increased over baseline at day 1 in both cohorts and remained higher in cohort 2 until day 30. CD45+CD133+ progenitor cells decreased over baseline at day 30 in cohort 1. We identified specific cell subpopulations associated with improved cardiac function in patients with chronic LV dysfunction. These findings may improve patient selection and prediction of outcomes in cell therapy trials.
Highlights
Heart failure (HF) affects more than 38 million patients globally and poses enormous challenges for health care systems worldwide [1, 2]
We sought to investigate whether changes in peripheral blood (PB)-derived circulatory cell subpopulations collected at different time-points and demographic parameters measured at baseline could predict improved left ventricular ejection fraction (LVEF), VO2 max, and left ventricular endsystolic volume (LVESV) in heart failure (HF) patients regardless of treatment
The best functional outcome was defined as an increase in LVEF and VO2 max and a decrease in LVESV, whereas the worst outcome was defined as a decrease in LVEF and VO2 max, and an increase in LVESV (Figure 1)
Summary
Heart failure (HF) affects more than 38 million patients globally and poses enormous challenges for health care systems worldwide [1, 2]. We previously reported that a subset of patients in the FOCUS-CCTRN trial showed improved LVEF, maximal oxygen consumption (VO2 max), and left ventricular endsystolic volume (LVESV). In this patient subgroup, improvement in the three outcomes was associated with an increase in bone marrow CD19+ B cells, CD11b+ monocytes, CD31dim cell subsets, and CXCR4+ migratory cells and a reduction in CD31bright cells compared with patients who had no change or a worsening in any of the three outcomes [7, 8]. It is not known if this cell population profile persists in the peripheral blood (PB)
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