Identification of distinct phenotypic clusters in heart failure with preserved ejection fraction

Alicia Uijl*, Gianluigi Savarese, Ilonca Vaartjes, Ulf Dahlström, Jasper J. Brugts, Gerard C.M. Linssen, Vanessa van Empel, Hans Peter Brunner-La Rocca, Folkert W. Asselbergs, Lars H. Lund, Arno W. Hoes, Stefan Koudstaal

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Aims: We aimed to derive and validate clinically useful clusters of patients with heart failure with preserved ejection fraction (HFpEF; left ventricular ejection fraction ≥50%). 

Methods and results: We derived a cluster model from 6909 HFpEF patients from the Swedish Heart Failure Registry (SwedeHF) and externally validated this in 2153 patients from the Chronic Heart Failure ESC-guideline based Cardiology practice Quality project (CHECK-HF) registry. In SwedeHF, the median age was 80 [interquartile range 72–86] years, 52% of patients were female and most frequent comorbidities were hypertension (82%), atrial fibrillation (68%), and ischaemic heart disease (48%). Latent class analysis identified five distinct clusters: cluster 1 (10% of patients) were young patients with a low comorbidity burden and the highest proportion of implantable devices; cluster 2 (30%) patients had atrial fibrillation, hypertension without diabetes; cluster 3 (25%) patients were the oldest with many cardiovascular comorbidities and hypertension; cluster 4 (15%) patients had obesity, diabetes and hypertension; and cluster 5 (20%) patients were older with ischaemic heart disease, hypertension and renal failure and were most frequently prescribed diuretics. The clusters were reproduced in the CHECK-HF cohort. Patients in cluster 1 had the best prognosis, while patients in clusters 3 and 5 had the worst age- and sex-adjusted prognosis. 

Conclusions: Five distinct clusters of HFpEF patients were identified that differed in clinical characteristics, heart failure drug therapy and prognosis. These results confirm the heterogeneity of HFpEF and form a basis for tailoring trial design to individualized drug therapy in HFpEF patients.

Original languageEnglish
Pages (from-to)973-982
Number of pages10
JournalEuropean Journal of Heart Failure
Volume23
Issue number6
Early online date29 Mar 2021
DOIs
Publication statusPublished - Jun 2021

Bibliographical note

Funding Information:
This study was supported by grants to LHL's institution from the Swedish Research Council [grants 2013‐23897‐104604‐23 and 523‐2014‐2336], the Swedish Heart Lung Foundation [grants 20150557 and 20170841], and the Stockholm County Council [grant 20140220, 20170112]. F. W. Asselbergs is supported by UCL Hospitals NIHR Biomedical Research Centre. I.V. is supported by the Dutch Heart Foundation, as part of ‘Facts and Figures’.

Funding Information:
The Swedish Heart Failure Registry is funded by the Swedish National Board of Health and Welfare, the Swedish Association of Local Authorities and Regions, the Swedish Society of Cardiology, and the Swedish Heart-Lung Foundation. Servier, the Netherlands, partially funded the inclusion of data and software program for CHECK-HF. The CHECK-HF steering committee (J.B., G.L., H.P.B.L.R., A.H.) received no funding for this project. The current study was initiated by the authors and was designed, conducted, interpreted, and reported independently of the sponsor. This work has received support from the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant n? 116074. This study was supported by grants to LHL's institution from the Swedish Research Council [grants 2013-23897-104604-23 and 523-2014-2336], the Swedish Heart Lung Foundation [grants 20150557 and 20170841], and the Stockholm County Council [grant 20140220, 20170112]. F. W. Asselbergs is supported by UCL Hospitals NIHR Biomedical Research Centre. I.V. is supported by the Dutch Heart Foundation, as part of ?Facts and Figures?. Conflict of interest: G.S. reports grants and personal fees from Vifor, AstraZeneca, grants and non-financial support from Boehringer Ingelheim, personal fees from SPA, Roche, grants from MSD, outside the submitted work. H.P.B.L.R. reports non-financial support from Servier, during the conduct of the study; grants and personal fees from Novartis, Vifor, Roche Diagnostics, Medtronic, outside the submitted work; and collaboration in INTERREG-NWE project with eHealth/AI companies (Sananet NL, Exploris CH). J.B. reports grants and personal fees from Vifor and Abbott not related to this project. U.D. reports grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Vifor, Boston Scientific and Roche Diagnostics and personal fees from Novartis, AstraZeneca and Amgen, outside the submitted work. L.H.L. reports personal fees from Merck, Sanofi, AstraZeneca, Bayer, Pharmacosmos, Abbott, Medscape, grants and personal fees from Boehringer Ingelheim, Vifor-Fresenius, Relypsa, Novartis, Mundipharma, grants from Boston Scientific, outside the submitted work. All other authors have nothing to disclose.

Funding Information:
: G.S. reports grants and personal fees from Vifor, AstraZeneca, grants and non‐financial support from Boehringer Ingelheim, personal fees from SPA, Roche, grants from MSD, outside the submitted work. H.P.B.L.R. reports non‐financial support from Servier, during the conduct of the study; grants and personal fees from Novartis, Vifor, Roche Diagnostics, Medtronic, outside the submitted work; and collaboration in INTERREG‐NWE project with eHealth/AI companies (Sananet NL, Exploris CH). J.B. reports grants and personal fees from Vifor and Abbott not related to this project. U.D. reports grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Vifor, Boston Scientific and Roche Diagnostics and personal fees from Novartis, AstraZeneca and Amgen, outside the submitted work. L.H.L. reports personal fees from Merck, Sanofi, AstraZeneca, Bayer, Pharmacosmos, Abbott, Medscape, grants and personal fees from Boehringer Ingelheim, Vifor‐Fresenius, Relypsa, Novartis, Mundipharma, grants from Boston Scientific, outside the submitted work. All other authors have nothing to disclose. Conflict of interest

Funding Information:
The Swedish Heart Failure Registry is funded by the Swedish National Board of Health and Welfare, the Swedish Association of Local Authorities and Regions, the Swedish Society of Cardiology, and the Swedish Heart‐Lung Foundation. Servier, the Netherlands, partially funded the inclusion of data and software program for CHECK‐HF. The CHECK‐HF steering committee (J.B., G.L., H.P.B.L.R., A.H.) received no funding for this project. The current study was initiated by the authors and was designed, conducted, interpreted, and reported independently of the sponsor. This work has received support from the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant n° 116074.

Publisher Copyright:
© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

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