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Machine learning based on biomarker profiles identifies distinct subgroups of heart failure with preserved ejection fraction.

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journal contribution
posted on 09.09.2021, 09:33 by Rebecca J Woolley, Daan Ceelen, Wouter Ouwerkerk, Jasper Tromp, Sylwia M Figarska, Stefan D Anker, Kenneth Dickstein, Gerasimos Filippatos, Faiez Zannad, Metra Marco, Leong Ng, Nilesh Samani, Dirk van Veldhuisen, Chim Lang, Carolyn S Lam, Adriaan Voors

Aims

The lack of effective therapies for patients with heart failure with preserved ejection fraction (HFpEF) is often ascribed to the heterogeneity of patients with HFpEF. We aimed to identify distinct pathophysiologic clusters of HFpEF based on circulating biomarkers.

Methods and results

We performed an unsupervised cluster analysis using 363 biomarkers from 429 patient with HFpEF. Relative differences in expression profiles of the biomarkers between clusters were assessed and used for pathway over-representation analyses. We identified four distinct patients subgroups based on their biomarker profiles : cluster 1 with the highest prevalence of diabetes mellitus and renal disease; cluster 2 with oldest age and frequent age-related comorbidities; cluster 3 with youngest age, largest body size, least symptoms and lowest NT-proBNP levels; and cluster 4 with highest prevalence of ischemic aetiology, smoking and chronic lung disease, most symptoms, as well as highest NT-proBNP and troponin levels. Over a median follow-up of 21 months, the occurrence of death or HF hospitalization was highest in clusters 1 and 4 (62.1% and 62.8% respectively) and lowest in cluster 3 (25.6%). Pathway over-representation analyses revealed that the biomarker profile of patients in cluster 1 was associated with activation of inflammatory pathways while the biomarker profile of patients in cluster 4 was specifically associated with pathways implicated in cell proliferation regulation and cell survival.

Conclusion

Unsupervised cluster analysis based on biomarker profiles identified mutually exclusive subgroups of patients with HFpEF with distinct biomarker profiles, clinical characteristics and outcomes, suggesting different underlying pathophysiological pathways. This article is protected by copyright. All rights reserved.

History

Citation

European Journal of Heart Failure (2021) 23, 983–991

Author affiliation

Department of Cardiovascular Sciences, University of Leicester

Version

VoR (Version of Record)

Published in

European journal of heart failure

Volume

23

Issue

6

Pagination

983-991

Publisher

Wiley

issn

1388-9842

eissn

1879-0844

Acceptance date

26/02/2021

Copyright date

2021

Available date

09/09/2021

Spatial coverage

England

Language

eng