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Identifying Pathophysiological Mechanisms in Heart Failure With Reduced Versus Preserved Ejection Fraction.

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posted on 07.09.2018, 15:18 by Jasper Tromp, B. Daan Westenbrink, Wouter Ouwerkerk, Dirk J. van Veldhuisen, Nilesh J. Samani, Piotr Ponikowski, Marco Metra, Stefan D. Anker, John G. Cleland, Kenneth Dickstein, Gerasimos Filippatos, Pim van der Harst, Chim C. Lang, Leong L. Ng, Faiez Zannad, Aelko H. Zwinderman, Hans L. Hillege, Petervan van der Meer, Adriaan A. Voors
BACKGROUND: Information on the pathophysiological differences between heart failure with reduced ejection fraction (HFrEF) versus heart failure with preserved ejection fraction (HFpEF) is needed OBJECTIVES: The purpose of this study was to establish biological pathways specifically related to HFrEF and HFpEF. METHODS: The authors performed a network analysis to identify unique biomarker correlations in HFrEF and HFpEF using 92 biomarkers from different pathophysiological domains in a cohort of 1,544 heart failure (HF) patients. Data were independently validated in 804 patients with HF. Networks were enriched with existing knowledge on protein-protein interactions and translated into biological pathways uniquely related to HFrEF, HF with a midrange ejection fraction, and HFpEF. RESULTS: In the index cohort (mean age 74 years; 34% female), 718 (47%) patients had HFrEF (left ventricular ejection fraction [LVEF] <40%) and 431 (27%) patients had HFpEF (LVEF ≥50%). A total of 8 (12%) correlations were unique for HFrEF and 6 (9%) were unique to HFpEF. Central proteins in HFrEF were N-terminal B-type natriuretic peptide, growth differentiation factor-15, interleukin-1 receptor type 1, and activating transcription factor 2, while central proteins in HFpEF were integrin subunit beta-2 and catenin beta-1. Biological pathways in HFrEF were related to DNA binding transcription factor activity, cellular protein metabolism, and regulation of nitric oxide biosynthesis. Unique pathways in patients with HFpEF were related to cytokine response, extracellular matrix organization, and inflammation. Biological pathways of patients with HF with a midrange ejection fraction were in between HFrEF and HFpEF. CONCLUSIONS: Network analysis showed that biomarker profiles specific for HFrEF are related to cellular proliferation and metabolism, whereas biomarker profiles specific for HFpEF are related to inflammation and extracellular matrix reorganization. (The BIOlogy Study to TAilored Treatment in Chronic Heart Failure [BIOSTAT-CHF]; EudraCT 2010-020808-29).

Funding

BIOSTAT-CHF was funded by the European Commission (FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29). Support was also provided by the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON2014-11 RECONNECT.

History

Citation

Journal of the American College of Cardiology, 2018, 72 (10), pp. 1081-1090

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

AM (Accepted Manuscript)

Published in

Journal of the American College of Cardiology

Publisher

Elsevier for American College of Cardiology

issn

0735-1097

eissn

1558-3597

Acceptance date

18/06/2018

Copyright date

2018

Available date

04/09/2019

Publisher version

https://www.sciencedirect.com/science/article/pii/S073510971835407X?via=ihub

Notes

The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.

Language

en

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