Clinical Gray Zones of Cardiac Troponin Interpretation in the Emergency Department: When Increased Concentrations Do Not Equal Acute Coronary Syndrome

The introduction of rapid, high-sensitivity cardiac troponin (hs-cTn)-based algorithms has markedly changed the work-up of patients admitted to the emergency department (ED) with suspected acute coronary syndrome (ACS). However, when applied to real-world ED populations, these algorithms perform worse than in clinical studies of derivation and validation. The main reasons for this discrepancy are that patients tested for hs-cTn in real-world settings tend to be older and less clinically preselected. Nevertheless, ACS must often be ruled out in patients with atypical presentations. Routine patients also more frequently have impaired renal function and pre-existing cardiac diseases, such as atrial fibrillation, heart failure, or coronary artery disease. These conditions do not necessarily cause the actual acute ED presentation. Using the standard decision limits of the 0 h, 0/1 h, or 0/2 h algorithms does not hinder the exclusion of ACS in the ED. However, using them in real-world conditions substantially decreases the positive predictive value for acute myocardial infarction (AMI) and classifies a higher percentage of patients into the “observe (gray) zone” than reported in clinical studies. Patients classified with a working diagnosis of “rule-in AMI” often require hospital admission for other reasons, though their discharge diagnosis may differ from AMI. A major challenge in real-world EDs is the high proportion of gray zone hs-cTn concentrations in approximately 50% of tested patients. Therefore, additional hs-cTn sampling at 3 h after admission is often necessary to rule out acute myocardial injury. This review summarizes and critically discusses the evidence for adjusting hs-cTn ED algorithm decision limits according to age, sex, and renal function. It also discusses the critical differential diagnosis of acute and chronic myocardial injury in the ED.