ObjectiveTo perform serial electrocardiogram (ECG) analyses in patients with subtle ECG changes in the anterior leads and evaluate the performance of the four-variable formula in detecting left anterior descending (LAD) coronary artery occlusion. MethodsThis prospective study included patients admitted to the emergency department with acute chest pain between April 2021 and January 2023, whose initial ECG was not diagnostic but indicated suspicion of myocardial infarction (MI) and who underwent percutaneous coronary intervention in their follow-up. The control group consisted of patients who were diagnosed with benign variant ST-segment elevation (BV-STE) due to ST-segment elevation (STE) of at least 1 mm in the anterior lead, who had normal cardiac troponin levels, and who presented with non-cardiac chest pain. Following admission, six ECGs were taken at 10-min intervals. The scores of all patients were calculated with the four-variable formula on serial ECGs and compared between the groups. ResultsA total of 232 patients, including 116 with anterior MI and 116 with BV-STE, were included in the study. When the cut-off value for the four-variable formula was taken as ≥18.2, the sensitivity, specificity, and diagnostic accuracy of the first ECG were determined to be 82.7%, 85.3%, and 83.6%, respectively. We found that the four-variable formula had the highest sensitivity, specificity, and diagnostic accuracy in detecting LAD occlusion for the ECG taken at the 20th minute (83.6%, 89.6%, and 86.2%, respectively). ConclusionThe four-variable formula was found to be a valid method for the differentiation of STEMI and BV-STE in patients with subtle ECG changes. While managing this patient group, using serial ECGs rather than a single ECG to evaluate the clinical status of patients can help clinicians make more accurate decisions.