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

Abstract : 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
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https://hal.univ-lorraine.fr/hal-03165434
Contributor : Erwan Bozec <>
Submitted on : Wednesday, March 10, 2021 - 4:24:41 PM
Last modification on : Friday, August 27, 2021 - 12:26:06 PM
Long-term archiving on: : Friday, June 11, 2021 - 7:10:10 PM

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Rebecca Woolley, Daan Ceelen, Wouter Ouwerkerk, Jasper Tromp, Sylwia Figarska, et al.. Machine learning based on biomarker profiles identifies distinct subgroups of heart failure with preserved ejection fraction. European Journal of Heart Failure, Oxford University Press (OUP), 2021, ⟨10.1002/ejhf.2144⟩. ⟨hal-03165434⟩

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