TY - JOUR
T1 - Identifying Pathophysiological Mechanisms in Heart Failure With Reduced Versus Preserved Ejection Fraction
AU - Tromp, Jasper
AU - Westenbrink, B Daan
AU - Ouwerkerk, Wouter
AU - van Veldhuisen, Dirk J
AU - Samani, Nilesh J
AU - Ponikowski, Piotr
AU - Metra, Marco
AU - Anker, Stefan D
AU - Cleland, John G
AU - Dickstein, Kenneth
AU - Filippatos, Gerasimos
AU - van der Harst, Pim
AU - Lang, Chim C
AU - Ng, Leong L
AU - Zannad, Faiez
AU - Zwinderman, Aelko H
AU - Hillege, Hans L
AU - van der Meer, Peter
AU - Voors, Adriaan A
N1 - Publisher Copyright:
© 2018
PY - 2018/9/4
Y1 - 2018/9/4
N2 - 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.
AB - 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.
KW - Activating Transcription Factor 2/metabolism
KW - Aged
KW - Biomarkers/metabolism
KW - CD18 Antigens/metabolism
KW - Female
KW - Growth Differentiation Factor 15/metabolism
KW - Heart Failure/metabolism
KW - Humans
KW - Male
KW - Natriuretic Peptide, Brain/metabolism
KW - Receptors, Interleukin-1 Type I/metabolism
KW - Stroke Volume/physiology
KW - Transcriptional Activation/physiology
KW - beta Catenin/metabolism
U2 - 10.1016/j.jacc.2018.06.050
DO - 10.1016/j.jacc.2018.06.050
M3 - Article
C2 - 30165978
SN - 0735-1097
VL - 72
SP - 1081
EP - 1090
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 10
ER -