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使用监督式机器学习模型预测原位肝移植后的主要不良心血管事件:一项队列研究。

Predicting major adverse cardiovascular events after orthotopic liver transplantation using a supervised machine learning model: A cohort study.

作者信息

Soldera Jonathan, Corso Leandro Luis, Rech Matheus Machado, Ballotin Vinícius Remus, Bigarella Lucas Goldmann, Tomé Fernanda, Moraes Nathalia, Balbinot Rafael Sartori, Rodriguez Santiago, Brandão Ajacio Bandeira de Mello, Hochhegger Bruno

机构信息

Post Graduate Program at Acute Medicine and Gastroenterology, University of South Wales, Cardiff CF37 1DL, United Kingdom.

Postgraduate Program in Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre 90050-170, Brazil.

出版信息

World J Hepatol. 2024 Feb 27;16(2):193-210. doi: 10.4254/wjh.v16.i2.193.

Abstract

BACKGROUND

Liver transplant (LT) patients have become older and sicker. The rate of post-LT major adverse cardiovascular events (MACE) has increased, and this in turn raises 30-d post-LT mortality. Noninvasive cardiac stress testing loses accuracy when applied to pre-LT cirrhotic patients.

AIM

To assess the feasibility and accuracy of a machine learning model used to predict post-LT MACE in a regional cohort.

METHODS

This retrospective cohort study involved 575 LT patients from a Southern Brazilian academic center. We developed a predictive model for post-LT MACE (defined as a composite outcome of stroke, new-onset heart failure, severe arrhythmia, and myocardial infarction) using the extreme gradient boosting (XGBoost) machine learning model. We addressed missing data (below 20%) for relevant variables using the k-nearest neighbor imputation method, calculating the mean from the ten nearest neighbors for each case. The modeling dataset included 83 features, encompassing patient and laboratory data, cirrhosis complications, and pre-LT cardiac assessments. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC). We also employed Shapley additive explanations (SHAP) to interpret feature impacts. The dataset was split into training (75%) and testing (25%) sets. Calibration was evaluated using the Brier score. We followed Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for reporting. Scikit-learn and SHAP in Python 3 were used for all analyses. The supplementary material includes code for model development and a user-friendly online MACE prediction calculator.

RESULTS

Of the 537 included patients, 23 (4.46%) developed in-hospital MACE, with a mean age at transplantation of 52.9 years. The majority, 66.1%, were male. The XGBoost model achieved an impressive AUROC of 0.89 during the training stage. This model exhibited accuracy, precision, recall, and F1-score values of 0.84, 0.85, 0.80, and 0.79, respectively. Calibration, as assessed by the Brier score, indicated excellent model calibration with a score of 0.07. Furthermore, SHAP values highlighted the significance of certain variables in predicting postoperative MACE, with negative noninvasive cardiac stress testing, use of nonselective beta-blockers, direct bilirubin levels, blood type O, and dynamic alterations on myocardial perfusion scintigraphy being the most influential factors at the cohort-wide level. These results highlight the predictive capability of our XGBoost model in assessing the risk of post-LT MACE, making it a valuable tool for clinical practice.

CONCLUSION

Our study successfully assessed the feasibility and accuracy of the XGBoost machine learning model in predicting post-LT MACE, using both cardiovascular and hepatic variables. The model demonstrated impressive performance, aligning with literature findings, and exhibited excellent calibration. Notably, our cautious approach to prevent overfitting and data leakage suggests the stability of results when applied to prospective data, reinforcing the model's value as a reliable tool for predicting post-LT MACE in clinical practice.

摘要

背景

肝移植(LT)患者年龄越来越大,病情也越来越重。LT后主要不良心血管事件(MACE)的发生率有所上升,这反过来又增加了LT后30天的死亡率。当应用于LT前的肝硬化患者时,非侵入性心脏应激测试会失去准确性。

目的

评估一种用于预测区域队列中LT后MACE的机器学习模型的可行性和准确性。

方法

这项回顾性队列研究纳入了来自巴西南部一个学术中心的575例LT患者。我们使用极端梯度提升(XGBoost)机器学习模型开发了一个用于预测LT后MACE(定义为中风、新发心力衰竭、严重心律失常和心肌梗死的综合结果)的预测模型。我们使用k近邻插补法处理相关变量的缺失数据(低于20%),为每个病例计算十个最近邻的平均值。建模数据集包括83个特征,涵盖患者和实验室数据、肝硬化并发症以及LT前的心脏评估。使用受试者操作特征曲线下面积(AUROC)评估模型性能。我们还采用Shapley加法解释(SHAP)来解释特征影响。数据集被分为训练集(75%)和测试集(25%)。使用Brier评分评估校准情况。我们遵循个体预后或诊断多变量预测模型的透明报告指南进行报告。所有分析均使用Python 3中的Scikit-learn和SHAP。补充材料包括模型开发代码和一个用户友好的在线MACE预测计算器。

结果

在纳入的537例患者中,23例(4.46%)发生了院内MACE,移植时的平均年龄为52.9岁。大多数患者(66.1%)为男性。XGBoost模型在训练阶段达到了令人印象深刻的0.89的AUROC。该模型的准确率、精确率、召回率和F1分数分别为0.84、0.85、0.80和0.79。通过Brier评分评估的校准表明模型校准良好,评分为0.07。此外,SHAP值突出了某些变量在预测术后MACE中的重要性,在队列水平上,非侵入性心脏应激测试结果为阴性、使用非选择性β受体阻滞剂、直接胆红素水平、O型血以及心肌灌注闪烁显像的动态改变是最有影响的因素。这些结果突出了我们的XGBoost模型在评估LT后MACE风险方面的预测能力,使其成为临床实践中的一个有价值的工具。

结论

我们的研究成功评估了XGBoost机器学习模型在使用心血管和肝脏变量预测LT后MACE方面的可行性和准确性。该模型表现出令人印象深刻的性能,与文献结果一致,并表现出良好的校准。值得注意的是,我们预防过拟合和数据泄露的谨慎方法表明,当应用于前瞻性数据时结果具有稳定性,这加强了该模型作为临床实践中预测LT后MACE的可靠工具的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc0/10941741/349148403ef3/WJH-16-193-g001.jpg

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