1. Pathophysiological insights into machine learning-based subphenotypes of acute heart failure with preserved ejection fraction.
- Author
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Sotomi Y, Tamaki S, Hikoso S, Nakatani D, Okada K, Dohi T, Sunaga A, Kida H, Sato T, Matsuoka Y, Sakamoto D, Kitamura T, Komukai S, Seo M, Yano M, Hayashi T, Nakagawa A, Nakagawa Y, Ohtani T, Yasumura Y, Yamada T, and Sakata Y
- Subjects
- Humans, Growth Differentiation Factor 15, Cystatin C, Stroke Volume physiology, Retrospective Studies, Prospective Studies, Biomarkers, Natriuretic Peptide, Brain, Inflammation, Peptide Fragments, Cardiomegaly, Prognosis, Heart Failure diagnosis
- Abstract
Objective: The heterogeneous pathophysiology of the diverse heart failure with preserved ejection fraction (HFpEF) phenotypes needs to be examined. We aim to assess differences in the biomarkers among the phenotypes of HFpEF and investigate its multifactorial pathophysiology., Methods: This study is a retrospective analysis of the PURSUIT-HFpEF Study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF. In this registry, there is a predefined subcohort in which we perform multibiomarker tests (N=212). We applied the previously established machine learning-based clustering model to the subcohort with biomarker measurements to classify them into four phenotypes: phenotype 1 (n=69), phenotype 2 (n=49), phenotype 3 (n=41) and phenotype 4 (n=53). Biomarker characteristics in each phenotype were evaluated., Results: Phenotype 1 presented the lowest value of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C reactive protein, tumour necrosis factor-α, growth differentiation factor (GDF)-15, troponin T and cystatin C, whereas phenotype 2, which is characterised by hypertension and cardiac hypertrophy, showed the highest value of these markers. Phenotype 3 showed the second highest value of GDF-15 and cystatin C. Phenotype 4 presented a low NT-proBNP value and a relatively high GDF-15., Conclusions: Distinctive characteristics of biomarkers in HFpEF phenotypes would indicate differential underlying mechanisms to be elucidated. The contribution of inflammation to the pathogenesis varied considerably among different HFpEF phenotypes. Systemic inflammation substantially contributes to the pathophysiology of the classic HFpEF phenotype with cardiac hypertrophy., Trial Registration Number: UMIN-CTR ID: UMIN000021831., Competing Interests: Competing interests: YSo has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical, TOA EIYO, Bristol-Myers Squibb, Biosense Webster, Abbott Medical Japan and NIPRO; and personal fees from Abiomed, AstraZeneca, Amgen Astellas BioPharma, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Abbott Medical Japan, Boston Scientific Japan, Bayer, Daiichi Sankyo, Novartis, TERUMO, Medtronic and Pfizer Pharmaceuticals. SH has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical and 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. YSa has received personal fees from Otsuka Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, AstraZeneca and Actelion Pharmaceuticals; and grants from Roche Diagnostic, FUJIFILM Toyama Chemical, Bristol-Myers Squibb Co, Biosense Webster, Abbott Medical Japan, Otsuka Pharmaceutical, Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation, Astellas Pharma, Kowa Company, Boehringer Ingelheim Japan and Biotronik., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
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