When to order a second cardiac troponin (cTn) level?

From the Guidelines

A second cardiac troponin test should be ordered 1-2 hours after the initial test in patients presenting with symptoms suggestive of acute coronary syndrome (ACS) using high-sensitivity troponin assays. This recommendation is based on the most recent and highest quality study, which suggests that the 0 h/1 h algorithm or the 0 h/2 h algorithm can be used for rapid "rule-in" and "rule-out" of MI 1. The use of high-sensitivity troponin assays allows for a shorter time interval to the second troponin assessment, improving diagnostic accuracy and enabling timely clinical decision-making.

Key Considerations

• The time-dependent release of troponin from damaged myocardial cells means that a single negative test cannot reliably exclude myocardial infarction, particularly in patients who present early after symptom onset.
• In patients with a high clinical suspicion of ACS but initial negative troponin, additional testing at 6-12 hours may be warranted.
• The interpretation of serial troponin values should focus on both the absolute values and the change (delta) between measurements, as significant changes can indicate acute myocardial injury even when values remain within normal reference ranges.
• Clinical variables such as age, renal dysfunction, and chest pain onset can affect high-sensitivity cardiac troponin concentrations, and should be taken into account when interpreting results 1.

Diagnostic Approach

• The 0 h/1 h algorithm or the 0 h/2 h algorithm can be used for rapid "rule-in" and "rule-out" of MI, with optimal thresholds for rule-out and rule-in selected to allow for a minimal sensitivity and NPV of 99% and a minimal PPV of 70% 1.
• High-sensitivity troponin assays are recommended over less sensitive ones, as they provide higher diagnostic accuracy at identical low cost 1.
• Other biomarkers, such as CK-MB and copeptin, may have clinical relevance in specific clinical settings, but their routine use is not recommended 1.

From the Research

Ordering a Second Cardiac Troponin (cTn) Level

When to order a second cardiac troponin (cTn) level is a critical decision in the diagnosis of acute myocardial infarction (AMI). The following points summarize the evidence:

• A second cTn level should be ordered 2 hours after the initial measurement in patients with suspected AMI, as a diagnostic algorithm incorporating high-sensitivity cardiac troponin T (hs-cTnT) values at presentation and absolute changes within the first 2 hours can safely rule out or accurately rule in AMI in the vast majority of patients 2.
• In high-risk patients with suspected acute coronary syndrome, a second standard troponin level can be ordered 2 hours after the initial measurement, as the negative predictive value of negative 2-hour troponins along with no significant delta troponin rise was 98.7% 3.
• Serial conventional cardiac troponin measurements 3-6 hours apart are recommended for non-ST-elevation MI (NSTEMI) diagnosis, and a second cTn level can be ordered 3 hours after the initial measurement to identify major adverse cardiac events (MACE) 4.
• In patients with chronic kidney disease (CKD), a second high-sensitivity troponin measurement can be ordered 3 hours after the initial measurement to improve the diagnostic performance of cardiac troponins for suspected NSTEMI 5.
• The timing of troponin testing is fundamental to its clinical utility, and a single troponin test is reasonable in primary care to exclude the possibility of acute myocardial infarction in asymptomatic low-risk patients whose symptoms resolved at least 12 hours prior 6.

Key Considerations

• The choice of troponin assay (high-sensitivity or conventional) and the timing of measurements depend on the clinical context and the patient's risk profile.
• Serial troponin measurements can improve the diagnostic performance of cardiac troponins, especially in patients with CKD or high-risk patients with suspected acute coronary syndrome.
• The use of a diagnostic algorithm incorporating troponin values and dynamic changes in troponin concentration can help rule in or out AMI in a significant proportion of patients.