Background: Patients with heart failure with reduced ejection fraction have a poor prognosis. The identification of subgroups with different outcomes and treatment response patterns may help to tailor strategies to each individual patient. We present an exploratory study of patients enrolled in the EMPHASIS-HF trial (Eplerenone in Patients With Systolic Heart Failure and Mild Symptoms) using latent class analysis with validation using the EPHESUS trial (Eplerenone, a Selective Aldosterone Blocker, in Patients With Left Ventricular Dysfunction After Myocardial Infarction) to identify subgroups of patients with different prognosis and response to eplerenone therapy.

Methods and Results: Latent class analysis identifies mutually exclusive groups of individuals maximizing within-group similarities and between-group differences. In the EMPHASIS-HF trial, 2279 heart failure with reduced ejection fraction patients were randomized to eplerenone or placebo and were characterized according to 18 clinical features. Subgroup definitions were applied to 6472 patients enrolled in the EPHESUS trial to validate observations. Event-free survival and effect of eplerenone on the composite of cardiovascular death and heart failure hospitalization were determined for each subgroup. Four subgroups were identified with significant differences in event-free survival (P=0.002). The subgroup C had the worst event-free survival in both studies and was characterized by older age, lower body mass index, worse renal function, higher baseline potassium levels, high prevalence of anemia, diabetes mellitus, previous revascularization and higher rates of eplerenone discontinuation, and hyperkalemia during follow-up. Two subgroups (B and C) showed a poorer response to eplerenone in both studies and these groups shared common features such as lower body mass index and high prevalence of anemia. Clinical profiles, prognosis, and treatment response patterns of the 4 subgroups applied in EPHESUS trial presented similarities to those observed in EMPHASIS.

Conclusions: Using a data-driven approach, we identified heart failure with reduced ejection fraction subgroups with significantly different prognoses and potentially different responses to eplerenone. However, these data should be regarded as hypothesis-generating and prospective validation is warranted, to assess the potential clinical implications of these subgroups.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00232180.

背景：射血分数降低的心力衰竭患者预后较差。识别具有不同结果和治疗反应模式的亚组可能有助于针对每个患者量身定制策略。我们使用EHPHASIS试验（依普利农，一种选择性醛固酮阻滞剂，依普利农，左心功能不全）对潜伏类分析进行了验证，对参与EMPHASIS-HF试验（收缩期心力衰竭和轻度症状的依普利酮）的患者进行了一项探索性研究。心肌梗塞后），以识别依普利酮治疗不同预后和反应的患者亚组。

方法和结果：潜在类别分析确定了互斥的个体群体，从而最大化了群体内的相似性和群体间的差异。在EMPHASIS-HF试验中，将2279例射血分数降低的心力衰竭患者随机分为依普利酮或安慰剂，并根据18种临床特征进行了特征分析。将亚组定义应用于参加EPHESUS试验的6472名患者，以验证观察结果。对于每个亚组，均确定了无事件生存率和依普利农对心血管死亡和心力衰竭住院的复合影响。四个亚组的无事件生存期存在显着差异（P= 0.002）。C组在两项研究中的无事件生存期最差，其特点是年龄大，体重指数低，肾功能差，基线钾水平升高，贫血患病率高，糖尿病，先前的血运重建和依普利农停药率更高以及随访期间的高钾血症。在两个研究中，两个亚组（B和C）对依普利农的反应较差，这些组具有共同的特征，例如较低的体重指数和较高的贫血患病率。EPHESUS试验中应用的4个亚组的临床概况，预后和治疗反应模式与EMPHASIS中观察到的相似。

结论：使用数据驱动的方法，我们确定了射血分数亚组减少的心力衰竭，其预后显着不同，对依普利农的反应也可能不同。但是，应将这些数据视为假设的产生者，并有必要进行前瞻性验证，以评估这些亚组的潜在临床意义。

临床试验注册： URL：https://www.clinicaltrials.gov。唯一标识符：NCT00232180。