Please use this identifier to cite or link to this item:
Title: Novel endotypes in heart failure: effects on guideline-directed medical therapy
Authors: Tromp, J
Ouwerkerk, W
Demissei, BG
Anker, SD
Cleland, JG
Dickstein, K
Filippatos, G
van der Harst, P
Hillege, HL
Lang, CC
Metra, M
Ng, LL
Ponikowski, P
Samani, NJ
van Veldhuisen, DJ
Zannad, F
Zwinderman, AH
Voors, AA
van der Meer, P
First Published: 13-Dec-2018
Publisher: Oxford University Press (OUP) for European Society of Cardiology
Citation: Eur Heart J, 2018, 39 (48), pp. 4269-4276
Abstract: Aims: We sought to determine subtypes of patients with heart failure (HF) with a distinct clinical profile and treatment response, using a wide range of biomarkers from various pathophysiological domains. Methods and results: We performed unsupervised cluster analysis using 92 established cardiovascular biomarkers to identify mutually exclusive subgroups (endotypes) of 1802 patients with HF and reduced ejection fraction (HFrEF) from the BIOSTAT-CHF project. We validated our findings in an independent cohort of 813 patients. Based on their biomarker profile, six endotypes were identified. Patients with endotype 1 were youngest, less symptomatic, had the lowest N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and lowest risk for all-cause mortality or hospitalization for HF. Patients with endotype 4 had more severe symptoms and signs of HF, higher NT-proBNP levels and were at highest risk for all-cause mortality or hospitalization for HF [hazard ratio (HR) 1.4; 95% confidence interval (CI) 1.1-1.8]. Patients with endotypes 2, 3, and 5 were better uptitrated to target doses of beta-blockers (P < 0.02 for all). In contrast to other endotypes, patients with endotype 5 derived no potential survival benefit from uptitration of angiotensin-converting enzyme-inhibitor/angiotensin-II receptor blocker and beta-blockers (Pinteraction <0.001). Patients with endotype 2 (HR 1.29; 95% CI 1.10-1.42) experienced possible harm from uptitration of beta-blockers in contrast to patients with endotype 4 and 6 that experienced benefit (Pinteraction for all <0.001). Results were strikingly similar in the independent validation cohort. Conclusion: Using unsupervised cluster analysis, solely based on biomarker profiles, six distinct endotypes were identified with remarkable differences in characteristics, clinical outcome, and response to uptitration of guideline directed medical therapy.
DOI Link: 10.1093/eurheartj/ehy712
eISSN: 1522-9645
Embargo on file until: 13-Dec-2019
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © The Author(s), 2018. Deposited with reference to the publisher’s open access archiving policy. (
Description: 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.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

Files in This Item:
File Description SizeFormat 
submission manuscript_final_version.pdfPost-review (final submitted author manuscript)2.12 MBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.