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Peripheral Blood Biomarkers Associated With Improved Functional Outcome in Patients With Chronic Left Ventricular
Lourdes Chacon Alberty1, Emerson C Perin2, James T Willerson2
1Regenerative Medicine Department, Texas Heart Institute, Houston, TX, United States.
Insights
Specific immune cell changes in peripheral blood correlate with heart failure treatment outcomes. Identifying these cell subpopulations may improve patient selection for future cell therapies.
Area of Science:
- Immunology
- Cardiology
- Regenerative Medicine
Background:
- Cell therapy for heart failure (HF) shows variable results, with unclear mechanisms for patient response.
- Immune cell roles in HF progression and treatment are not fully understood.
- Understanding immune dynamics is crucial for optimizing cell therapy efficacy.
Purpose of the Study:
- To investigate associations between changes in peripheral blood cell subpopulations and functional outcomes in chronic ischemic cardiomyopathy patients.
- To compare immune cell profiles in patients with the best versus worst outcomes after cell therapy or placebo.
- To identify specific immune cell markers predictive of treatment response in HF.
Main Methods:
- Analysis of peripheral blood samples collected at multiple time points (days 0, 1, 30, 90, 180) from the FOCUS-CCTRN trial.
- Flow cytometry used to quantify 32 distinct peripheral blood cell subpopulations.
- Linear mixed-effects models applied to assess temporal changes and compare patient cohorts with differing functional outcomes.
Main Results:
- Patients with improved cardiac function (Cohort 1) showed a higher frequency of CD45+CD19+ B cells compared to those with poorer outcomes (Cohort 2).
- CD11B+ cells transiently increased in both cohorts, remaining elevated longer in Cohort 2.
- CD45+CD133+ progenitor cells decreased by day 30 in the improved outcome group (Cohort 1).
Conclusions:
- Specific peripheral blood cell subpopulations are associated with improved cardiac function post-cell therapy.
- Findings suggest potential biomarkers for predicting treatment response in heart failure patients.
- This research may guide patient selection and outcome prediction in future cell therapy trials for heart failure.
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.
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