Methods: We prospectively enrolled 112 patients with HFrEF defined by New York Heart Association (NYHA) functional class >II and left ventricular ejection fraction (LVEF) <40%. Patients were stratified in ischemic (iHFrEF, n=57) and dilated etiology (dHFrEF, n=55). Cells from fresh heparinized blood were stained and analyzed using BD FACS Canto II flow cytometry. Cox regression hazard analysis was used to assess the influence of Tregs on survival. The multivariate model was adjusted forage and gender.
Results: Comparing patients with iHFrEF to dHFrEF 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). Interestingly while there was no association with cardiovascular survival independently in the dHFrEFsubgroup (adj. HR per 1-SD of 0.62 (95% CI 0.17-2.31); p=0.486), we found a significant inverse association of Tregs and cardiovascular survival in patients with iHFrEFwith an adj. HR per 1-SD of 0.59 (95% CI 0.36-0.96; p=0.034).
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.
Figure 1: Survival Curves of Cardiovascular Mortality.Kaplan-Meier plots showing survival free of cardiovascular mortality in the total study collective (A) and patients stratified in ischemic CMP (B) as well dilative CMP (C) according to tertiles of frequencies of regulatory T cells. Tertile 1 = high; Tertile 2 = mid; Tertile 3 = low