When should troponin be repeated in patients with suspected acute coronary syndrome (ACS) and a negative initial result?

Troponin Testing Protocol in Suspected Acute Coronary Syndrome

Troponin should be repeated beyond 6 hours after symptom onset in patients with initially normal serial troponins if they have electrocardiographic changes and/or intermediate/high risk clinical features. 1

Initial Troponin Testing

• Cardiac-specific troponin (troponin I or T) levels should be measured at presentation and 3-6 hours after symptom onset in all patients with suspected ACS to identify a rising and/or falling pattern 1
• If the time of symptom onset is ambiguous or unclear, the time of presentation should be considered the time of onset for assessing troponin values 1
• Contemporary troponin assays are the preferred markers for diagnosis of ACS; CK-MB and myoglobin are not useful and should not be ordered 1

When to Repeat Troponin Beyond Initial Testing

Indications for Additional Troponin Testing:

• Additional troponin levels should be obtained beyond 6 hours after symptom onset in patients with normal troponins on serial examination when: 1
  • Electrocardiographic changes are present (such as ST-segment depression, T-wave inversion)
  • Clinical presentation confers an intermediate or high index of suspicion for ACS

Risk Stratification to Guide Decision-Making:

• Use validated risk scores (such as TIMI or GRACE) to assess prognosis and determine the need for additional troponin testing 1, 2
• High-risk features warranting additional troponin testing include: 1
  • Age ≥65 years
  • ≥3 risk factors for CAD
  • Prior coronary stenosis ≥50%
  • ST deviation on ECG
  • ≥2 anginal events in prior 24 hours
  • Use of aspirin in prior 7 days

Observation Protocol

• It is reasonable to observe patients with symptoms consistent with ACS but without objective evidence of myocardial ischemia (nonischemic initial ECG and normal cardiac troponin) in a chest pain unit or telemetry unit with serial ECGs and cardiac troponin at 3-6 hour intervals 1
• For patients presenting within 6 hours of symptom onset, a delta change in troponin of >30% between serial measurements improves specificity for diagnosis of AMI 3

Special Considerations

• High-sensitivity troponin assays may allow for earlier rule-out of myocardial infarction, but serial testing remains important to detect significant changes 4, 5
• In patients with a high clinical suspicion but negative initial troponins, consider continuous cardiac monitoring with 12-lead ECG as a reasonable alternative 1
• The presence and magnitude of troponin elevations are useful for both short-term and long-term prognosis 1

Follow-up Troponin Testing

• It may be reasonable to remeasure troponin once on day 3 or day 4 in patients with confirmed MI as an index of infarct size and dynamics of necrosis 1
• B-type natriuretic peptide (BNP) may be considered for additional prognostic information in patients with suspected ACS 1

Common Pitfalls to Avoid

• Failing to repeat troponin in patients with high-risk features despite initially negative results 1
• Relying solely on troponin without considering the clinical context and ECG findings 1
• Using outdated biomarkers like CK-MB and myoglobin which add no diagnostic value with contemporary troponin assays 1
• Not allowing sufficient time between serial troponin measurements to detect significant changes 5, 3

Remember that troponin testing is just one component of the evaluation of patients with suspected ACS, and decisions regarding additional testing should be guided by the overall clinical presentation, ECG findings, and risk stratification.