Identification of Distinct Phenotypic Clusters in Heart Failure with Preserved Ejection Fraction

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

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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
Issue number6
Early online date29 Mar 2021
Publication statusPublished - Jun 2021


  • Clusters
  • Comorbidities
  • External validation
  • Heart failure with preserved ejection fraction
  • Latent class analysis
  • Phenotyping
  • Treatment


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