Novel endotypes in heart failure: effects of guideline-directed medical therapy

Tromp, J. et al. (2018) Novel endotypes in heart failure: effects of guideline-directed medical therapy. European Heart Journal, (Accepted for Publication)

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Abstract

Background: 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. Method 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 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 (HR 1.4; 95%CI 1.1-1.8). Patients with endotypes 2, 3 and 5 were better up-titrated 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 ACEi/ARB 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.

Item Type:Articles
Additional Information:BIOSTAT-CHF was funded by the European Commission [FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29]
Status:Accepted for Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cleland, Professor John
Authors: Tromp, J., Ouwerkerk, W., Demissei, B.G., Anker, S.D., Cleland, J.G., Dickstein, K., Filippatos, G., van der Harst, P., Hillege, H.L., Lang, C.C., Metra, M., Ng, L.L., Ponikowski, P., Samani, N.J., van Veldhuisen, D.J., Zannad, F., Zwinderman, A.H., Voors, A.A., and van der Meer, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:European Heart Journal
Publisher:Oxford University Press
ISSN:0195-668X
ISSN (Online):1522-9645

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