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Background: To determine the rate of all cause and cardiac death, new myocardial infarction (MI) or coronary revascularisation at over three years from index visit in emergency department chest pain patients without known coronary artery disease (CAD) at index presentation who had a negative electrocardiogram (ECG) and biomarker workup for acute coronary syndrome (ACS).Methods: An unplanned sub-study of a prospective observational study of consecutive adult patients presenting to the ED with atraumatic chest pain (or equivalents). The primary outcome of interest was the predictive performance of a negative ECG and biomarker work-up for ACS for all cause and cardiac mortality over more than three years' follow-up in patients not known to have pre-existing CAD presenting to the ED with chest pain. Secondary outcomes were rate of new MI or revascularisation not related to the index visit.Results: 237 patients were studied. Median age was 52 years (IQR 42 - 62) and 55.3% were male. Median follow-up was 48 months. There were seven deaths (3%, 95% CI 1.4 - 6%), one of which was potentially cardiac in origin with cause of death given as pulmonary hypertension and cardiac failure (0.4%, 95% CI 0.02 - 2.3%). There was one confirmed MI (0.6%, 95% CI 0.03 - 3.8%). The rate of revascularisation not related to the index visit was 3.1% (95% CI 1.1 - 7.4%).Conclusion: Patients who present to ED with potentially cardiac chest pain but who do not have known CAD, and have non-ischaemic ECGs and troponin assays below the 99th percentile are at low risk of cardiac death or MI in long-term follow-up. This challenges the recommendation for routine functional or anatomic testing. [ABSTRACT FROM AUTHOR]