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Development of an ensemble machine learning prognostic model to predict 60-day risk of major adverse cardiac events in adults with chest pain

By Chris J Kennedy, Dustin G. Mark, Jie Huang, Mark J. van der Laan, Alan E Hubbard, Mary E. Reed

Posted 08 Mar 2021
medRxiv DOI: 10.1101/2021.03.08.21252615

Background: Chest pain is the second leading reason for emergency department (ED) visits and is commonly identified as a leading driver of low-value health care. Accurate identification of patients at low risk of major adverse cardiac events (MACE) is important to improve resource allocation and reduce over-treatment. Objectives: We assessed machine learning (ML) methods and electronic health record (EHR) covariate collection for MACE prediction. We aimed to maximize the pool of low-risk patients that were accurately predicted to have less than 0.5% MACE risk and could be eligible for reduced testing ("rule-out" strategy). Population Studied: 116,764 adult patients presenting with chest pain in the ED between 2013 and 2015 and evaluated for potential acute coronary syndrome (ACS). 60-day MACE rate was 2%. Setting: Data analysis was performed May 2018 to August 2021. Methods: We evaluated ML algorithms (lasso, splines, random forest, extreme gradient boosting, Bayesian additive regression trees) and SuperLearner stacked ensembling. We tuned ML hyperparameters through nested ensembling, and imputed missing values with generalized low-rank models (GLRM). Performance was benchmarked against individual biomarkers, validated clinical risk scores, decision trees, and logistic regression. We assessed clinical utility through net benefit analysis and explained the models through variable importance ranking and accumulated local effect visualization Results: The SuperLearner ensemble provided the best cross-validated discrimination with areas under the curve of 0.15 for precision-recall (PR-AUC) and 0.87 for receiver operating characteristic (ROC-AUC), and the best accuracy with an index of prediction accuracy of 0.07. The ensemble's risk estimates were miscalibrated by 0.2 percentage points on average, and dominated the net benefit analysis at all examined thresholds. At a 0.5% threshold the ensemble model yielded 32 benefit-adjusted workups avoided per 100 patients, compared to 25 for logistic regression and 2-14 for clinical risk scores. The most important predictors were age, troponin, clinical risk scores, and electrocardiogram. GLRM achieved a 90% average reduction in reconstruction error compared to median-mode imputation. Conclusion: Combining ML algorithms with a broad set of EHR covariates improved MACE risk prediction and would reduce over-treatment compared to simpler alternatives, while providing calibrated predictions and interpretability. Patients should receive targeted benefit in their care from thorough detection of nuanced health patterns via ML.

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