TY - JOUR
T1 - Identifying Pathophysiological Mechanisms in Heart Failure With Reduced Versus Preserved Ejection Fraction
AU - Tromp, Jasper
AU - Westenbrink, Daan
AU - Ouwerkerk, Wouter
AU - van Veldhuisen, Dirk Jan
AU - Samani, Nilesh J.
AU - Ponikowski, Piotr
AU - Metra, Marco
AU - Anker, Stefan D.
AU - Cleland, John G. F.
AU - Dickstein, Kenneth
AU - Filippatos, Gerasimos S.
AU - van der Harst, Pim
AU - Lang, Chim
AU - Ng, Leong Loke
AU - Zannad, Faiez
AU - Zwinderman, Aelko H.
AU - Hillege, Hans L.
AU - van der Meer, Peter
AU - Voors, Adriaan A.
N1 - Funding: BIOSTAT-CHF was funded by the European Commission [FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29]. We acknowledge the support from the Netherlands Cardiovascular Research Initiative: An initiative with support of the Dutch Heart Foundation, CVON2014-11 RECONNECT.
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. (The BIOlogy Study to TAilored Treatment in Chronic Heart Failure [BIOSTAT-CHF]; EudraCT 2010-020808-29)
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. (The BIOlogy Study to TAilored Treatment in Chronic Heart Failure [BIOSTAT-CHF]; EudraCT 2010-020808-29)
KW - HFpEF
KW - HFrEF
KW - network analysis
KW - pathophysiology
KW - biomarkers
UR - http://www.scopus.com/inward/record.url?scp=85051778661&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2018.06.050
DO - 10.1016/j.jacc.2018.06.050
M3 - Article
C2 - 30165978
AN - SCOPUS:85051778661
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 -