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

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:72

Article

Tromp, Jasper^1,2,3  Westenbrink, B. Daan¹  Ouwerkerk, Wouter⁴  van Veldhuisen, Dirk J.¹  Samani, Nilesh J.^5,6  Ponikowski, Piotr^7,8  Metra, Marco⁹  Anker, Stefan D.^10,11  Cleland, John G.¹²  Dickstein, Kenneth¹³  Filippatos, Gerasimos¹⁴  van der Harst, Pim¹  Lang, Chim C.¹⁵  Ng, Leong L.^5,6  Zannad, Faiez¹⁶  Zwinderman, Aelko H.⁴  Hillege, Hans L.¹  van der Meer, Peter¹  Voors, Adriaan A.¹ 

[1] Univ Groningen, Dept Cardiol, Groningen, Netherlands

[2] Natl Heart Ctr Singapore, Singapore, Singapore

[3] Duke NUS Med Sch, Singapore, Singapore

[4] Acad Med Ctr, Dept Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands

[5] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England

[6] Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England

[7] Wroclaw Med Univ, Dept Heart Dis, Wroclaw, Poland

[8] Mil Hosp, Cardiol Dept, Wroclaw, Poland

[9] Univ Brescia, Dept Med & Surg Specialties, Inst Cardiol, Radiol Sci & Publ Hlth, Brescia, Italy

[10] Charite, Dept Cardiol CVK, Div Cardiol & Metab Heart Failure, Cachexia & Sarcopenia, Berlin, Germany

[11] Charite, Berlin Brandenburg Ctr Regenerat Therapies BCRT, Berlin, Germany

[12] Univ Glasgow, Glasgow Royal Infirm, Robertson Ctr Biostat, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland

[13] Univ Bergen, Stavanger Univ Hosp, Stavanger, Norway

[14] Univ Athens, Athens Univ Hosp Attikon, Sch Med, Dept Cardiol,Heart Failure Unit, Athens, Greece

[15] Univ Dundee, Div Mol & Clin Med, Dundee, Scotland

[16] Univ Lorrain, CHU Nancy, INSERM CIC 1433, Nancy, France

关键词: biomarkers;    HFpEF;    HFrEF;    network analysis;    pathophysiology;   

DOI  :  10.1016/j.jacc.2018.06.050

来源: Elsevier

【 摘 要 】

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 inHFrEF andHFpEF 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) (C) 2018 Published by Elsevier on behalf of the American College of Cardiology Foundation.

【 授权许可】

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