Author + information
- Received December 16, 2016
- Revision received April 10, 2017
- Accepted April 14, 2017
- Published online June 26, 2017.
- Jasper Tromp, MDa,
- Mohsin A.F. Khan, PhDa,b,
- Robert J. Mentz, MDc,
- Christopher M. O’Connor, MDd,
- Marco Metra, MDe,
- Howard C. Dittrich, MDf,
- Piotr Ponikowski, MDg,
- John R. Teerlink, MDh,
- Gad Cotter, MDi,
- Beth Davison, PhDi,
- John G.F. Cleland, MDj,
- Michael M. Givertz, MDk,
- Daniel M. Bloomfield, MDl,
- Dirk J. Van Veldhuisen, MD, PhDa,
- Hans L. Hillege, PhDa,m,
- Adriaan A. Voors, MD, PhDa,∗ ( and )
- Peter van der Meer, MD, PhDa
- aDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- bHeart Failure Research Centre, Academic Medical Centre, Amsterdam, the Netherlands
- cDuke University Medical Center, Durham, North Carolina
- dInova Heart and Vascular Institute, Falls Church, Virginia
- eUniversity of Brescia, Brescia, Italy
- fCardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, Iowa
- gMedical University, Clinical Military Hospital, Wroclaw, Poland
- hUniversity of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California
- iMomentum Research, Durham, North Carolina
- jUniversity of Hull, Kingston upon Hull, United Kingdom
- kBrigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- lMerck & Co., Inc., Kenilworth, New Jersey
- mDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- ↵∗Address for correspondence:
Dr. Adriaan A. Voors, Department of Cardiology, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, the Netherlands.
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)
The PROTECT trial was supported by NovaCardia, a subsidiary of Merck & Co. Dr. Cleland was on the Steering Committee (and received payment) for the PROTECT trial; served on the advisory board (and received payment) for MSD. Dr. O’Connor is a consultant to Merck & Co., Inc. Dr. Ponikowski has received honoraria from Merck & Co., Inc. Drs. Davison and Cotter are employees of Momentum Research Inc., which was contracted to perform work on the project by Merck & Co., Inc. Dr. Metra has received honoraria and reimbursements from NovaCardia (sponsor of the study) and Merck & Co., Inc. Dr. Givertz has received institutional research support and served on a scientific advisory board for Merck & Co., Inc. Dr. Teerlink has received research funds and consulting fees from Merck & Co., Inc. Dr. Bloomfield is an employee of Merck & Co., Inc. Dr. Dittrich served as a consultant to Merck & Co., Inc. Dr. Voors has received speaker and consultancy fees from Merck & Co., Inc.; was on the Steering Committee for the PROTECT trial; and received research support from Alere, Singulex, and Sphingotec. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Barry H. Greenberg, MD, served as Guest Editor for this article.
- Received December 16, 2016.
- Revision received April 10, 2017.
- Accepted April 14, 2017.
- 2017 American College of Cardiology Foundation