Phenotyping of acute decompensated heart failure with preserved ejection fraction
Yohei Sotomi, Shungo Hikoso, Sho Komukai, Taiki Sato, Bolrathanak Oeun, Tetsuhisa Kitamura, Akito Nakagawa, Daisaku Nakatani, Hiroya Mizuno, Katsuki Okada, Tomoharu Dohi, Akihiro Sunaga, Hirota Kida, Masahiro Seo, Masamichi Yano, Takaharu Hayashi, Yusuke Nakagawa, Shunsuke Tamaki, Tomohito Ohtani, Yoshio Yasumura, Takahisa Yamada, Yasushi Sakata
Abstract
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.