High-Sensitivity Cardiac Troponin and the 2021 Guidelines for Acute Chest Pain

Sandoval Y, Apple FS, Mahler SA, on behalf of the International Federation of Clinical Chemistry and Laboratory Medicine Committee on the Clinical Application of Cardiac Biomarkers.
High-Sensitivity Cardiac Troponin and the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guidelines for the Evaluation and Diagnosis of Acute Chest Pain. Circulation 2022;Jul 1:[Epub ahead of print].

This primer discusses the use of high-sensitivity cardiac troponin (hs-cTn) testing in context of the 2021 multisociety guidelines for the evaluation and diagnosis of acute chest pain, with a notable focus on analytical aspects of the hs-cTn assays and their implications. The tables are the most informative aspect of this article and are worth reviewing. The following are 10 key points to remember:

  1. High-sensitivity troponin assays are the preferred biomarker for the detection of myocardial injury. Levels are reported in ng/L. The assay-specific 99th percentile upper reference limit is the threshold for the diagnosis of myocardial injury.
  2. The benefits of hs-cTn assays are that they expedite the evaluation of patients with suspected acute coronary syndrome through early identification of low-risk patients eligible for early discharge.
  3. The 99th percentile upper reference limit of hs-cTn assays is derived from samples of male and female participants presumed healthy through screening. These limits that define normality are thus dependent on the rigor of the screening criteria. They are not standardized and vary across assay.
  4. The 99th percentile upper reference limit is sex-specific, with women typically having lower 99th percentiles than men. The impact of using sex-specific reference limits on outcomes is unclear.
  5. The limit of detection of an hs-cTn assay is the lowest concentration of the analyte that can be detected. The limit of quantitation (LoQ) is the lower concentration of the analyte of which certainty can be quantified (i.e., with a coefficient of variation of 20%). The hs-cTn assays are only Food and Drug Administration–cleared to report the LoQ. These are often close in value.
  6. There are robust data supporting the recommendation that a single hs-cTn value < LoQ can rule out a myocardial infarction in patients presenting >2 hours after symptom onset. A single positive hs-cTn value >99th percentile upper reference limit is sensitive for but not specific for myocardial infarction, for which diagnosis my require serial testing.
  7. The pattern change in hs-cTn values (deltas) is also assay-specific. Interpretation of the delta needs to account for other clinical data such as the history (notably the onset of symptoms), electrocardiography changes, and imaging.
  8. In patients with chronically elevated hs-cTn, the absence of significant change defined as <20% delta is indicative of chronic myocardial injury.
  9. Unstable angina is diagnosed much less frequently in the era of hs-cTn, while the major increase in diagnosis of myocardial infarction is attributed to type 2 events.
  10. Rapid hs-cTn algorithms can fail in patients who present too early (<2 hours), as levels of hs-cTn may not have risen yet, or in those who present late (>12 hours), when a declining pattern can be noted. Interpretation in a clinical context is and will always be necessary.

Clinical Topics: Acute Coronary Syndromes, Noninvasive Imaging, ACS and Cardiac Biomarkers

Keywords: Acute Coronary Syndrome, Angina, Unstable, Biomarkers, Chest Pain, Diagnostic Imaging, Electrocardiography, Limit of Detection, Patient Discharge, Troponin

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