P4418Temporal analysis of leukocyte extravasation and morphological activation after standard cardiopulmonary exercise testing in patients with heart failure with reduced ejection fraction

Abstract

Abstract Introduction Long-term exercise training reduces the systemic inflammatory load in patients with cardiovascular diseases. Acutely, however, an exercise challenge can trigger pro-inflammatory responses. The underlying cardiac syndrome might also influence the response of the adaptive and innate immune system to an acute exercise challenge. Purpose We compared the acute response to a standardized cardiopulmonary exercise test (CPET) in patients with heart failure with reduced ejection fraction (HFrEF) and age matched controls. Methods Patients with HFrEF (n=8; left ventricular ejection fraction [LVEF] ≤40%) and controls (n=9, LVEF ≥50%) participated in a CPET. Blood samples were taken before, immediately after and 2 hours after the test. Quantitative and morphological changes in leukocyte subpopulations, and formation of leukocyte-platelet aggregates were assessed in fresh blood samples by flow cytometry. Results are given as median and inter-quartile range (IQR). Results HFrEF (mean LVEF: 34%) and controls (mean LVEF: 57%) were 59 (range: 41 to 80) and 57 (range: 50 to 65) years old, respectively. In both groups acute exercise increased total leukocytes per mL of blood (control: 1.37-fold [IQR: 1.16 to 1.49]; HFrEF: 1.24-fold [IQR: 1.20 to 1.32]), relative abundance of circulating NK cells (controls: 2.11-fold [IQR: 1.30 to 3.13]; HFrEF: 1.67-fold [IQR: 1.56 to 1.71] and NK-T cells (control: 1.69-fold [IQR: 1.52 to 3.60]; HFrEF: 1.62-fold [IQR: 1.60 to 2.53]). Contrarily, only in HFrEF patients CD4+ (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]) were augmented. Circulating monocyte and neutrophil numbers did not change in response to CPET. 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-exercise in HFrEF patients, but not in controls. Conclusion Patients with HFrEF show a differential leukocyte response to an acute exercise challenge, with an increase in T-lymphocyte abundance, a degranulation response in the intermediate monocyte subpopulation and an increased formation of neutrophil-platelet-aggregates compared to control subjects. Our data suggest differences in release and organ-homing of innate versus adaptive immune cells, thus underlining the importance of inter-organ communication in the acute adaption to physical exertion in HFrEF.