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

Background Underlying inflammation has been increasingly recognized in heart failure with a preserved ejection fraction ( HF p EF ). In this study we tested the hypothesis that pro‐inflammatory biomarkers are elevated in patients with acutely decompensated HF p EF ( AD ‐ HF p EF ) compared with patients with stable HF p EF (S‐ HF p EF ). 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 ( PTX 3) and clinical, demographic, echocardiographic‐Doppler and clinical outcomes data were analyzed in HF p EF patients enrolled in NHLBI Heart Failure Research Network clinical trials which enrolled patients with either AD ‐ HF p EF or S‐ HF p EF . Compared to S‐ HF p EF , AD ‐ HF p EF patients had higher levels of PTX 3 (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 PTX 3 levels were significantly higher in AD ‐ HF p EF compared with S‐ HF p EF patients admitted for decompensated HF within the previous year. PTX 3 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 ‐ HF p EF compared with S‐ HF p EF patients. PTX 3 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 ‐ HF p EF .