Prompt identification of acute coronary syndrome is a challenge in clinical practice. The 12lead electrocardiogram (ECG) is readily available during initial patient evaluation, but current rule-based interpretation approaches lack sufficient accuracy. Here we report machine learning-based methods for the prediction of underlying acute myocardial ischemia in patients with chest pain. Using 554 temporal-spatial features of the 12-lead ECG, we train and test multiple classifiers on two independent prospective patient cohorts (n = 1244). While maintaining higher negative predictive value, our final fusion model achieves 52% gain in sensitivity compared to commercial interpretation software and 37% gain in sensitivity compared to experienced clinicians. Such an ultra-early, ECG-based clinical decision support tool, when combined with the judgment of trained emergency personnel, would help to improve clinical outcomes and reduce unnecessary costs in patients with chest pain.

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Background Classical ST‐T waveform changes on standard 12‐lead ECG have limited sensitivity in detecting acute coronary syndrome (ACS) in the emergency department. Numerous novel ECG features have been previously proposed to augment clinicians' decision during patient evaluation, yet their clinical utility remains unclear. Methods and Results This was an observational study of consecutive patients evaluated for suspected ACS (Cohort 1 n=745, age 59±17, 42% female, 15% ACS; Cohort 2 n=499, age 59±16, 49% female, 18% ACS). Out of 554 temporal‐spatial ECG waveform features, we used domain knowledge to select a subset of 65 physiology‐driven features that are mechanistically linked to myocardial ischemia and compared their performance to a subset of 229 data‐driven features selected by multiple machine learning algorithms. We then used random forest to select a final subset of 73 most important ECG features that had both data‐ and physiology‐driven basis to ACS prediction and compared their performance to clinical experts. On testing set, a regularized logistic regression classifier based on the 73 hybrid features yielded a stable model that outperformed clinical experts in predicting ACS, with 10% to 29% of cases reclassified correctly. Metrics of nondipolar electrical dispersion (ie, circumferential ischemia), ventricular activation time (ie, transmural conduction delays), QRS and T axes and angles (ie, global remodeling), and principal component analysis ratio of ECG waveforms (ie, regional heterogeneity) played an important role in the improved reclassification performance. Conclusions We identified a subset of novel ECG features predictive of ACS with a fully interpretable model highly adaptable to clinical decision support applications. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT04237688.

Patients with occlusion myocardial infarction (OMI) and no ST-elevation on presenting electrocardiogram (ECG) are increasing in numbers. These patients have a poor prognosis and would benefit from immediate reperfusion therapy, but, currently, there are no accurate tools to identify them during initial triage. Here we report, to our knowledge, the first observational cohort study to develop machine learning models for the ECG diagnosis of OMI. Using 7,313 consecutive patients from multiple clinical sites, we derived and externally validated an intelligent model that outperformed practicing clinicians and other widely used commercial interpretation systems, substantially boosting both precision and sensitivity. Our derived OMI risk score provided enhanced rule-in and rule-out accuracy relevant to routine care, and, when combined with the clinical judgment of trained emergency personnel, it helped correctly reclassify one in three patients with chest pain. ECG features driving our models were validated by clinical experts, providing plausible mechanistic links to myocardial injury.

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