Huang Lexin, Dou Zixuan, Fang Fang, Zhou Boda, Zhang Ping, Jiang Rui
Department of Automation, Tsinghua University, Beijing, China.
School of Medicine, Tsinghua University, Beijing, China.
Comput Biol Med. 2025 Mar;186:109635. doi: 10.1016/j.compbiomed.2024.109635. Epub 2025 Jan 7.
Prognosis prediction in the intensive care unit (ICU) traditionally relied on physiological scoring systems based on clinical indicators at admission. Electrocardiogram (ECG) provides easily accessible information, with heart rate variability (HRV) derived from ECG showing prognostic value. However, few studies have conducted a comprehensive analysis of HRV-based prognostic model against established standards, which limits the application of HRV's prognostic value in clinical settings. This study aims to evaluate the utility of HRV in predicting mortality in the ICU. Additionally, we analyzed the applicability and interpretability of the HRV-integrated clinical model and identified the HRV factors that are most significant for patient prognosis.
A total of 2838 patients from the MIMIC-III database were retrospectively included in this study. These patients were randomly divided into training and testing sets at a 4:1 ratio. We collected 86 HRV indicators from patients' lead II ECG readings between 0.5h and 2h before the time of death in the ICU of deceased patients or time of discharge from the ICU of alive patients, in addition to 9 clinical parameters upon admission. Subsequently, machine learning models were developed by algorithms including logistic regression (LR), Random Forest (RF), Adaptive Boosting (Adaboost), Gradient Boost (GB), eXtreme Gradient Boosting (XGB), and Light GBM (LGB) algorithms. An ensemble model that integrated these six algorithms, along with a deep neural network model, was also explored. The ten most important variables were identified using the Shapley method. Subsequently, an HRV-modified clinical scoring system was constructed through recursive feature elimination.
The study demonstrated that the integrated model, utilizing both clinical and HRV features, outperformed the model based solely on clinical information in XGB, LGB and LR algorithms (p = 0.005-0.03). The ensemble model exhibited the best performance (AUROC = 0.878), followed closely by XGB algorithm (AUROC = 0.869). Both of these models significantly outperformed the APS III scoring system (AUROC = 0.765). Notably, this improvement is not dependent on a specific disease but rather on the timing of ECG recordings that are closer to clinical endpoints. For parameter analysis, Shapley's method identified MSEn, SD1SD2, DFAα1, and DFAα2 as key HRV features in predicting mortality. These variables also showed significant differences in univariate analysis across patients with different clinical outcomes (p < 0.0001). Additionally, regardless of machine learning, the additive scoring system incorporating HRV showed a significant enhancement in prognostic ability compared to traditional physiological scores APS III (p = 0.02).
The integration of HRV features into mortality prediction models has been shown to enhance predictive performances in ICU. This enhancement is not limited to specific machine learning models or diseases but is influenced by the timing of HRV measurement relative to clinical endpoints. HRV features, when combined with other clinical parameters, offer high interpretability and significant prognostic value. Furthermore, incorporating HRV into traditional ICU scoring systems can lead to improved predictive performance.
重症监护病房(ICU)中的预后预测传统上依赖于基于入院时临床指标的生理评分系统。心电图(ECG)可提供易于获取的信息,从ECG得出的心率变异性(HRV)具有预后价值。然而,很少有研究针对既定标准对基于HRV的预后模型进行全面分析,这限制了HRV预后价值在临床环境中的应用。本研究旨在评估HRV在预测ICU患者死亡率方面的效用。此外,我们分析了整合HRV的临床模型的适用性和可解释性,并确定了对患者预后最重要的HRV因素。
本研究回顾性纳入了MIMIC-III数据库中的2838例患者。这些患者以4:1的比例随机分为训练集和测试集。我们除了收集患者入院时的9项临床参数外,还在已故患者ICU死亡前0.5小时至2小时或存活患者从ICU出院时,从患者的II导联心电图读数中收集了86项HRV指标。随后,通过逻辑回归(LR)、随机森林(RF)、自适应增强(Adaboost)、梯度提升(GB)、极端梯度提升(XGB)和轻量级梯度提升机(LGB)算法开发机器学习模型。还探索了一个整合这六种算法的集成模型以及一个深度神经网络模型。使用Shapley方法确定了十个最重要的变量。随后,通过递归特征消除构建了一个HRV修正的临床评分系统。
研究表明,在XGB、LGB和LR算法中,利用临床和HRV特征的整合模型优于仅基于临床信息的模型(p = 0.005 - 0.03)。集成模型表现最佳(AUROC = 0.878),紧随其后的是XGB算法(AUROC = 0.869)。这两种模型均显著优于急性生理与慢性健康状况评分系统III(APS III,AUROC = 0.765)。值得注意的是,这种改进并不依赖于特定疾病,而是取决于更接近临床终点的心电图记录时间。对于参数分析,Shapley方法确定MSEn、SD1SD2、DFAα1和DFAα2是预测死亡率的关键HRV特征。这些变量在不同临床结局患者的单因素分析中也显示出显著差异(p < 0.0001)。此外,无论采用何种机器学习方法,纳入HRV的加法评分系统与传统生理评分APS III相比,预后能力都有显著提高(p = 0.02)。
将HRV特征整合到死亡率预测模型中已被证明可提高ICU中的预测性能。这种提高不限于特定的机器学习模型或疾病,而是受HRV测量时间相对于临床终点的影响。HRV特征与其他临床参数结合时,具有较高的可解释性和显著的预后价值。此外,将HRV纳入传统的ICU评分系统可提高预测性能。