Objective The pathophysiological heterogeneity of heart failure with preserved ejection fraction (HFpEF) makes the conventional ‘one-size-fits-all’ treatment approach difficult. We aimed to develop a stratification methodology to identify distinct subphenotypes of acute HFpEF using the latent class analysis.
Methods We established a prospective, multicentre registry of acute decompensated HFpEF. Primary candidates for latent class analysis were patient data on hospital admission (160 features). The patient subset was categorised based on enrolment period into a derivation cohort (2016–2018; n=623) and a validation cohort (2019–2020; n=472). After excluding features with significant missingness and high degree of correlation, 83 features were finally included in the analysis.
Results The analysis subclassified patients (derivation cohort) into 4 groups: group 1 (n=215, 34.5%), characterised by arrythmia triggering (especially atrial fibrillation) and a lower comorbidity burden; group 2 (n=77, 12.4%), with substantially elevated blood pressure and worse classical HFpEF echocardiographic features; group 3 (n=149, 23.9%), with the highest level of GGT and total bilirubin and frequent previous hospitalisation for HF and group 4 (n=182, 29.2%), with infection-triggered HF hospitalisation, high C reactive protein and worse nutritional status. The primary end point—a composite of all-cause death and HF readmission—significantly differed between the groups (log-rank p<0.001). These findings were consistent in the validation cohort.
Conclusions This study indicated the feasibility of clinical application of the latent class analysis in a highly heterogeneous cohort of patients with acute HFpEF. Patients can be divided into 4 phenotypes with distinct patient characteristics and clinical outcomes.
Trial registration number UMIN000021831.
- heart failure with preserved ejection fraction
Data availability statement
No data are available. Our study data will not be made available to other researchers for purposes of reproducing the results because of institutional review board restrictions.
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Contributors Concept and design: YSo, SH, SK, TS, BO, TK, AN and YSa. Data analysis and statistical analysis: YSo, SK and TS. Manuscript draft: YSo, SH, SK, TS, BO, TK, AN and YSa. Critical revision, editing and approval of the final manuscript: all authors. Guarantor: YSo, SH, and YSa.
Funding This work was funded by Roche Diagnostics K.K. and Fuji Film Toyama Chemical Co. Ltd.
Competing interests YSo has received personal fees from Daiichi-Sankyo, Bayer, Boehringer Ingelheim and Bristol-Myers Squibb. SH has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical, Actelion Pharmaceuticals; and personal fees from Daiichi-Sankyo, Astellas Pharma, Bayer, Pfizer Pharmaceuticals, Boehringer Ingelheim Japan, Kowa Company and Ono Pharmaceutical. DN has received personal fees from Roche Diagnostics. HM is an endowed chair lecturer supported by Asahi Intecc, Terumo Corporation, Nipro Corporation and Shimadzu Corporation, and has received personal fees from Medtronic Japan, Japan Tobacco, Pfizer Japan, Bayer Yakuhin, Japan Lifeline, Abbott Japan, Nippon Boehringer Ingelheim, Toa Eiyo, Daiichi-Sankyo and Kowa. KO has received personal fees from Bayer. YSa has received personal fees from Otsuka Pharmaceutical, Ono Pharmaceutical, Daiichi-Sankyo, Mitsubishi Tanabe Pharma, AstraZeneca and Actelion Pharmaceuticals, and grants from Roche Diagnostic, FUJIFILM Toyama Chemical, Bristol-Myers Squibb, Biosense Webster, Abbott Medical Japan, Otsuka Pharmaceutical, Daiichi-Sankyo, Mitsubishi Tanabe Pharma, Astellas Pharma, Kowa Company, Boehringer Ingelheim Japan and Biotronik.
Provenance and peer review Not commissioned; externally peer reviewed.
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