Rapid Use of High-sensitive Cardiac Troponin I for ruling-in and Ruling-out of Acute Myocardial Infarction

Background: Chest pain is a key symptom of acute coronary syndrome (ACS), but can also represent other cardiac and non-cardiac diseases. Rapid identification of ACS in terms of 'rule-in' or 'rule-out' is essential in order to minimize treatment delay and time to discharge. In the absence of ST-segment elevation myocardial infarction (STEMI) at initial ACS evaluation, the European Society of Cardiology guidelines recommend repeated measurements of high-sensitive cardiac troponin (hs-cTn) at presentation (0h) and 3 hours (3h) after presentation to rule-in and rule-out myocardial infarction (MI). An accelerated algorithm for ruling-in and ruling-out MI after 1h (0h/1h algorithm) has recently been suggested by the European Society of Cardiology as a valid alternative to the standard approach. The novel 0h/1h algorithm has only been validated for certain hs-cTn assays. However, routine use of the 0h/1h algorithm is still not widely implemented, as further data on algorithm performance are warranted.

A study of patients undergoing transcoronary ablation of septal hypertrophy, a clinical model of MI, shows that troponin concentrations measured by a hs-cTn assay significantly increase already after 15 minutes. This indicates that it may be possible to evaluate troponin dynamics even earlier than suggested by the 0h/1h algorithm. So far, no large-scale studies have included measurements of hs-cTn at 30m, and no 0h/30m algorithm has been derived. Therefore it is unknown if rule-in and rule-out of MI can be done safely using a 0h/30m algorithm.

Aim: To investigate if a high-sensitive Troponin Assay can rule-in or rule-out MI, when using a 0h/30m and a 0h/1h algorithm.

Patients and methods: This prospective cohort study will include patients presenting to the Emergency Department with chest pain suggestive of ACS. The study is designed to enroll 1.000 patients with complete blood samples (0h, 30m, 1h and 3h).

The expected incidence of MI in our population is inevitably low due to pre-hospital risk-stratification based on point-of-care troponin and electrocardiogram evaluation in the ambulance. Thus, patients with a very high pre-test probability of MI will be admitted to tertiary care centers with cardiac catheterization facilities rather than a regional hospital as in present study. Pilot study calculations estimate an expected prevalence of MI in our study cohort of approximately 7.4%. Assuming a negative predictive value of 99.7% in the rule-out group, a distribution with 7% patients in the rule-in group and 20% assigned to the observational zone (patients who can't be stratified to either the rule-out or the rule-in group), enrolment of at least 500 patients for derivation of the algorithms and at least 500 for the validation of the respective algorithms will provide an acceptable lower boundary of 98.2% of the two-sided 95% confidence interval.