Altered compositions of monocyte, T lymphocyte and NK cell subsets in heart failure of adult congenital heart disease

Adults with congenital heart disease (ACHD) display changes in adaptive immunity related to early open-heart surgery and subsequent incidental thymectomy. In acquired heart failure (HF) systemic inflammation, innate and adaptive immune cells play an important role. However, cellular immune alterations of monocyte, T lymphocyte and natural killer (NK) cell subsets have not been related to HF in ACHD.

Altered immune cell compositions related to heart failure and exhibited prognostic relevance. This suggests an important link between immunity, inflammation and HF in ACHD bearing potential for refined clinical risk stratification.

This cross-sectional study included 209 ACHD outpatients (mean age: 35.3 ± 11.0 years; NYHA class I/II/III-IV 64.1%/21.5%/14.4%; 59.8% male) and 21 healthy controls (29.8 ± 12.6 years; 47.6% male). Patients with clinical signs of infection, inflammatory diseases or malignancies were excluded. Flow cytometry of fresh whole blood revealed significantly elevated levels of CD14++CD16+ (Mon2) and CD14+CD16++ (Mon3) monocytes that increased in advanced NYHA class. Immature CD14+HLA-DRneg/low monocytes were significantly higher in ACHD, but did not relate to NT-proBNP or NYHA class. Frequencies of Mon2, CD14+HLA-DRneg/low and neutrophils related to plasma S100A8/A9 levels. Furthermore, ACHD had decreased T helper and cytotoxic T cell counts, however NKT and CD3bright T cells remained unchanged compared to control. The cytokine-producing CD56bright NK subset related to NT-proBNP and expanded in advanced HF stages. Patients with elevated Mon2 and CD14+HLA-DRneg/low monocytes exhibited a worse outcome regarding all-cause mortality/cardiac decompensations after a mean follow-up of 5.5 years. High Mon2, low total lymphocyte and low T helper cell counts were independent prognostic markers for the onset of adverse cardiac events. Conclusions: Altered immune cell compositions related to heart failure and exhibited prognostic relevance. This suggests an important link between immunity, inflammation and HF in ACHD bearing potential for refined clinical risk stratification.