The Immune Response To Cardiorespiratory Exercise Testing In Heart Failure Patients With Reduced Ejection Fraction

Abstract

PURPOSE: Long-term exercise training reduces systemic inflammation in heart failure patients. However, due to the impaired immune system in these patients, an acute exercise challenge may trigger pro-inflammatory responses. We compared the acute response to a standardized cardiopulmonary exercise test (CPET) in patients with heart failure with reduced ejection fraction (HFrEF) to age and gender matched controls. METHODS: Patients with HFrEF (n=13; left ventricular ejection fraction [LVEF] < 40%) and controls (n=14, LVEF > 50%) participated in a CPET. Blood samples were taken before, immediately after and 2 hours after CPET. Flow cytometry was used to assess quantitative and morphological alterations in leukocyte subpopulations as well as the formation of leukocyte-platelet aggregates. Only significant findings are reported (p < 0.05) and are given as median and inter-quartile range (IQR). RESULTS: HFrEF (mean LVEF: 36%) and controls (mean LVEF: 57%) were 59 (range: 41 to 80) and 57 (range: 50 to 65) years old, respectively. CPET increased the leukocyte (control: 1.37-fold [IQR: 1.16 to 1.49]; HFrEF: 1.24-fold [IQR: 1.20 to 1.32]), natural killer (NK) cell (controls: 2.11-fold [IQR: 1.30 to 3.13]; HFrEF: 1.67-fold [IQR: 1.56 to 1.71]) and NK-T cell (control: 1.69-fold [IQR: 1.52 to 3.60]; HFrEF: 1.62-fold [IQR: 1.60 to 2.53]) concentration in the HFrEF and control group. CD4+ cells (control: 1.15-fold [IQR: 0.84 to 1.54]; HFrEF: 1.45-fold [IQR: 1.10 to 1.98]) and CD8+ T-cells (control: 1.33-fold [IQR: 1.01 to 1.68]; HFrEF: 1.70-fold [IQR: 1.25 to 2.15]) only increased in HFrEF patients. Aggregation of thrombocytes with monocytes (control: 0.86-fold [IQR: 0.78 to 1.49]; HFrEF: 1.59-fold [IQR: 1.05 to 7.30-fold]), T-lymphocytes (control: 1.27-fold [IQR: 1.05 to 1.68]; HFrEF: 1.49-fold [IQR: 1.03 to 2.64]) and neutrophils (control: 1.08-fold [IQR: 0.87 to 1.25]; HFrEF: 2.13-fold [IQR: 1.62 to 2.19]) increased 2 hour post CPET in patients with HFrEF, but not in controls. CONCLUSIONS: CPET differentially induced specific immune responses in patients with HFrEF compared to age and gender matched controls. The prolonged immune response in these patients suggests differences in immune resolving mechanisms which deserve further research.