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Chronic heart failure (CHF) is characterized by hemodynamic compromise, neurohormonal and immune activation. We sought to examine the presence and severity of immunosenescence and its relation with the stages of CHF.We enrolled 86 consecutive stable systolic CHF patients and examined the relationship of leukocyte and lymphocyte subpopulation counts by flow cytometry with their functional status according to New York Heart Association (NYHA) class.Patients with advanced heart failure were characterized by significantly increased neutrophil and reduced lymphocyte counts. T-helper cells were increased, whereas B-cells and T cytotoxic cells were decreased. T-helper cells exhibited significant differentiation and aging across the NYHA classes; naïve T-cells, CD4 + CD45RA +, were significantly reduced in NYHA Class IV and memory T-cells, CD4 + CD45RO +, were significantly increased.Patients with CHF develop intense T-cell differentiation and aging. The presence of significant immunosenescence in advanced CHF may indicate a population at increased risk for adverse events.