Pro-Inflammatory Biomarkers in Stable Versus Acutely Decompensated Heart Failure With Preserved Ejection Fraction

J Am Heart Assoc. 2018 Apr 12;7(8):e007385. doi: 10.1161/JAHA.117.007385.

Abstract

Background: Underlying inflammation has been increasingly recognized in heart failure with a preserved ejection fraction (HFpEF). In this study we tested the hypothesis that pro-inflammatory biomarkers are elevated in patients with acutely decompensated HFpEF (AD-HFpEF) compared with patients with stable HFpEF (S-HFpEF).

Methods and results: Using a post hoc analysis the serum biomarkers tumor necrosis factor-alpha, high-sensitivity C-reactive protein interleukin 6 and pentraxin 3 (PTX3) and clinical, demographic, echocardiographic-Doppler and clinical outcomes data were analyzed in HFpEF patients enrolled in NHLBI Heart Failure Research Network clinical trials which enrolled patients with either AD-HFpEF or S-HFpEF. Compared to S-HFpEF, AD-HFpEF patients had higher levels of PTX3 (3.08 ng/mL versus 1.27 ng/mL, P<0.0001), interleukin-6 (4.14 pg/mL versus 1.71 pg/mL, P<0.0001), tumor necrosis factor-alpha (11.54 pg/mL versus 8.62 pg/mL, P=0.0015), and high-sensitivity C-reactive protein (11.90 mg/dL versus 3.42 mg/dL, P<0.0001). Moreover, high-sensitivity C-reactive protein, interleukin-6 and PTX3 levels were significantly higher in AD-HFpEF compared with S-HFpEF patients admitted for decompensated HF within the previous year. PTX3 was positively correlated with left atrial volume index (r=0.41, P=0.0017) and left ventricular mass (r=0.26, P=0.0415), while tumor necrosis factor-alpha was inversely correlated with E/A ratio (r=-0.31, P=0.0395).

Conclusions: Levels of pro-inflammatory biomarkers are strikingly higher in AD-HFpEF compared with S-HFpEF patients. PTX3 and tumor necrosis factor-alpha are correlated with echocardiographic-Doppler evidence of diastolic dysfunction. Taken together these data support the concept that a heightened pro-inflammatory state has a pathophysiologic role in the development of AD-HFpEF.

Keywords: biomarker; decompensated heart failure; diastolic dysfunction; diastolic heart failure; ejection fraction; heart failure; pro‐inflammatory biomarkers.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Cytokines / blood*
  • Echocardiography, Doppler
  • Female
  • Follow-Up Studies
  • Heart Failure / blood*
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy
  • Heart Failure / physiopathology
  • Humans
  • Inflammation / blood*
  • Male
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Phosphodiesterase 5 Inhibitors / therapeutic use*
  • Prognosis
  • Prospective Studies
  • Serum Amyloid P-Component / metabolism*
  • Stroke Volume / physiology*

Substances

  • Biomarkers
  • Cytokines
  • Peptide Fragments
  • Phosphodiesterase 5 Inhibitors
  • Serum Amyloid P-Component
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • PTX3 protein
  • C-Reactive Protein