The Prognostic Impact Of Circulating Regulatory T Lymphocytes On Mortality In Patients With Ischemic Heart Failure With Reduced Ejection Fraction

Background. Heart failure with reduced ejection fraction (HFrEF) constitutes a global health issue. While proinflanunatory cytokines proved to have a pivotal role in the development and progression of HFrEF, less attention has been paid to the cellular immunity. Regulatory T lymphocytes (Tregs) seem to have an important role in the induction and maintenance of immune homeostasis. Therefore, we aimed to investigate the impact of Tregs on the outcome in HFrEF. Methods. We prospectively enrolled 112 patients with HFrEF and performed flow cytometry for cell phenotyping. Individuals were stratified in ischemic (iHFrEF, n = 57) and nonischemic etiology (niHFrEF, n = 55). Cox regression hazard analysis was used to assess the influence of Tregs on survival. Results. Comparing patients with iHFrEF to niHFrEF, we found a significantly lower fraction of Tregs within lymphocytes in the ischemic subgroup (0.42% vs. 0.56%; p = 0.009). After a mean follow-up time of 4.5 years, 32 (28.6%) patients died due to cardiovascular causes. We found that Tregs were significantly associated with cardiovascular survival in the entire study cohort with an adjusted HR per one standard deviation (1-SD) of 0.60 (95% CI: 0.39-0.92; p = 0.017). A significant inverse association of Tregs and cardiovascular mortality in patients with iHFrEF with an adj. HR per 1-SD of 0.59 (95% CI: 0.36-0.96; p = 0.034) has been observed, while this association was not evident in the nonischemic subgroup (adj. HR per 1-SD of 0.62 (95% CI: 0.17-2.31); p = 0.486). Conclusion. Our results indicate a potential influence of Tregs in the pathogenesis and progression of iHFrEF, fostering the implication of cellular immunity in iHFrEF pathophysiology and proving Tregs as a predictor for long-term survival among iHFrEF patients. A preview of this study has been presented at a meeting of the European Society of Cardiology earlier this year.