Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
National Heart Centre Singapore, Singapore.
Eur J Heart Fail. 2021 Jun;23(6):983-991. doi: 10.1002/ejhf.2144. Epub 2021 Mar 17.
The lack of effective therapies for patients with heart failure with preserved ejection fraction (HFpEF) is often ascribed to the heterogeneity of patients with HFpEF. We aimed to identify distinct pathophysiologic clusters of HFpEF based on circulating biomarkers.
We performed an unsupervised cluster analysis using 363 biomarkers from 429 patients with HFpEF. Relative differences in expression profiles of the biomarkers between clusters were assessed and used for pathway over-representation analyses. We identified four distinct patient subgroups based on their biomarker profiles: cluster 1 with the highest prevalence of diabetes mellitus and renal disease; cluster 2 with oldest age and frequent age-related comorbidities; cluster 3 with youngest age, largest body size, least symptoms and lowest N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels; and cluster 4 with highest prevalence of ischaemic aetiology, smoking and chronic lung disease, most symptoms, as well as highest NT-proBNP and troponin levels. Over a median follow-up of 21 months, the occurrence of death or heart failure hospitalization was highest in clusters 1 and 4 (62.1% and 62.8%, respectively) and lowest in cluster 3 (25.6%). Pathway over-representation analyses revealed that the biomarker profile of patients in cluster 1 was associated with activation of inflammatory pathways while the biomarker profile of patients in cluster 4 was specifically associated with pathways implicated in cell proliferation regulation and cell survival.
Unsupervised cluster analysis based on biomarker profiles identified mutually exclusive subgroups of patients with HFpEF with distinct biomarker profiles, clinical characteristics and outcomes, suggesting different underlying pathophysiological pathways.
射血分数保留的心力衰竭（HFpEF）患者缺乏有效治疗方法，通常归因于 HFpEF 患者的异质性。我们旨在基于循环生物标志物确定 HFpEF 的不同病理生理簇。
我们使用 429 例 HFpEF 患者的 363 种生物标志物进行了无监督聚类分析。评估了生物标志物之间在聚类之间表达谱的相对差异，并用于途径过度表达分析。我们根据生物标志物谱确定了四个不同的患者亚组：第 1 组糖尿病和肾脏疾病患病率最高；第 2 组年龄最大，常伴有年龄相关的合并症；第 3 组年龄最小，体型最大，症状最少，N 端脑利钠肽前体（NT-proBNP）水平最低；第 4 组缺血性病因、吸烟和慢性肺部疾病患病率最高，症状最多，NT-proBNP 和肌钙蛋白水平最高。在中位数为 21 个月的随访中，第 1 组和第 4 组（分别为 62.1%和 62.8%）的死亡或心力衰竭住院发生率最高，第 3 组（25.6%）发生率最低。途径过度表达分析显示，第 1 组患者的生物标志物谱与炎症途径的激活有关，而第 4 组患者的生物标志物谱与细胞增殖调节和细胞存活相关的途径特别相关。
基于生物标志物谱的无监督聚类分析确定了 HFpEF 患者具有不同生物标志物谱、临床特征和结局的相互排斥亚组，提示存在不同的潜在病理生理途径。
