Biomarker Profiles of Acute Heart Failure Patients With a Mid-Range Ejection Fraction

Jasper Tromp, Mohsin A. F. Khan, Robert J. Mentz, Christopher M. O'Connor, Marco Metra, Howard C. Dittrich, Piotr Ponikowski, John R. Teerlink, Gad Cotter, Beth Davison, John G. F. Cleland, Michael M. Givertz, Daniel M. Bloomfield, Dirk J. Van Veldhuisen, Hans L. Hillege, Adriaan A. Voors*, Peter van der Meer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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OBJECTIVES In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction.

BACKGROUND Limited data are available on biomarker profiles in acute HFmrEF.

METHODS A panel of 37 biomarkers from different pathophysiological domains(e.g., myocardial stretch, inflammation, angiogenesis, oxidative stress, hematopoiesis) were measured at admission and after 24 h in 843 acute heart failure patients from the PROTECT trial. HFpEF was defined as left ventricular ejection fraction (LVEF) of >= 50% (n = 108), HFrEF as LVEF of <40% (n = 607), and HFmrEF as LVEF of 40% to 49% (n = 128).

RESULTS Hemoglobin and brain natriuretic peptide levels (300 pg/ml [HFpEF]; 397 pg/ml [HFmrEF]; 521 pg/ml [HFrEF]; ptrend <0.001) showed an upward trend with decreasing LVEF. Network analysis showed that in HFrEF interactions between biomarkers were mostly related to cardiac stretch, whereas in HFpEF, biomarker interactions were mostly related to inflammation. In HFmrEF, biomarker interactions were both related to inflammation and cardiac stretch. In HFpEF and HFmrEF ( but not in HFrEF), remodeling markers at admission and changes in levels of inflammatory markers across the first 24 h were predictive for all-cause mortality and rehospitalization at 60 days (pinteraction <0.05).

CONCLUSIONS Biomarker profiles in patients with acute HFrEF were mainly related to cardiac stretch and in HFpEF related to inflammation. Patients with HFmrEF showed an intermediate biomarker profile with biomarker interactions between both cardiac stretch and inflammation markers. (PROTECT-1: A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function; NCT00328692) (C) 2017 by the American College of Cardiology Foundation.

Original languageEnglish
Pages (from-to)507-517
Number of pages11
JournalJACC. Heart failure
Issue number7
Publication statusPublished - Jul-2017


  • acute heart failure
  • biomarkers
  • HFpEF
  • HFrEF

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