Inflammatory pathways in patients with heart failure and preserved ejection fraction

Immune activation is well established in patients with chronic heart failure and reduced ejection fraction (HF and reduced EF) and is associated with an impaired prognosis. Patients with heart failure and preserved ejection fraction (HF and preserved EF) have an impaired prognosis as well. It is not known whether they have signs of immune activation. Methods: We studied patients with HF and preserved EF (n = 17, NYHA II [n = 7]/III [n = 10]) and patients with HF and reduced EF (n = 17 NYHA II [n = 1]/III [n = 16]) and 20 controls. Echocardiography demonstrated preserved ejection fraction (LVEF 59 ± 9%), but LV hypertrophy in patients with preserved EF as compared with patients with reduced EF (LVEF 23 ± 5%). We evaluated levels of TNFα, its receptors (sTNFR-1 and 2), IL-6, IL-10 and NT-proBNP. Results: TNFα, was highest in HF with reduced EF (2.87 ± 0.65 vs 1.67 ± 0.58 pg/mL, p <0.001) compared to preserved EF and similar between HF with preserved EF and controls. However, sTNFR1 (1618 ± 384 vs 1017 ± 302 pg/mL, p <0.001) and sTNFR2 levels (3554 ± 916 vs 2041 ± 586 pg/mL, p <0.001) in HF with preserved EF were significantly higher compared with controls. The same was true for IL-6, IL-10 and NT-proBNP. The highest cytokine and NT-proBNP levels were present in HF with reduced EF. There was a negative correlation between TNFα, and LVEF (r = -  0.700; p <0.0001) and positive correlations between sTNFR1 and 2 with NT-proBNP. Conclusion: Patients with HF and preserved EF already show signs of systemic-immune activation which may contribute to the impaired prognosis and the progression to HF with reduced EF.