Major adverse cardiac events in patients with indeterminate high-sensitivity troponin testing and chest pain: a
Emma Helman1,2,3, Emily Brossard4, Jeremi Kolakowski4
1Faculty of Science, McGill University, Montreal, QC, Canada. emmaromany@gmail.com.
Insights
Elevated cardiac troponin levels in emergency departments may not indicate heart attack. Further research is needed to understand the major adverse cardiac events (MACE) risk in patients with indeterminate troponin results.
Area of Science:
- Cardiology
- Emergency Medicine
- Clinical Diagnostics
Background:
- High-sensitivity cardiac troponin (hs-cTn) assays detect low myocardial injury levels.
- Many emergency department (ED) chest pain patients exceed the 99th percentile limit without clear myocardial infarction (MI).
- Indeterminate hs-Tn results pose a management challenge.
Purpose of the Study:
- To systematically review and quantify the risk of major adverse cardiac events (MACE) in ED patients with single indeterminate hs-Tn measurements.
- To synthesize evidence on MACE in patients with troponin above the 99th percentile but below MI diagnostic cutoffs.
Main Methods:
- Systematic review of studies from MEDLINE, Cochrane, CINAHL, and EMBASE (2002-2025).
- Inclusion of studies reporting outcomes for indeterminate single hs-Tn measurements.
- Exclusion of patients with ECG findings indicative of STEMI or NSTEMI.
- Definition of MACE as MI, stroke, or cardiovascular mortality within 30 days.
Main Results:
- Eight studies (1 RCT, 3 prospective, 4 retrospective cohorts) involving 129,060 patients were included.
- MACE incidence ranged from 0.3% to 14.8%.
- 40% of eligible patients received a second troponin test; serial testing data remains limited.
- High risk of bias was noted in most observational studies.
Conclusions:
- The risk of MACE in patients with indeterminate hs-Tn and no serial testing is currently unknown.
- Over half of patients with indeterminate results did not undergo serial testing.
- Inconsistent management of indeterminate troponin results highlights the need for cautious interpretation and clinical assessment in low-risk patients.
Objectives:
Contemporary high-sensitivity cardiac troponin (hs-cTn) assays can detect very low levels of myocardial injury, leading many emergency department (ED) chest pain patients to exceed the 99th-percentile upper reference limit, despite low risk for myocardial infarction. This systematic review aimed to synthesize evidence quantifying the risk of MACE among ED patients with a single troponin concentration measurement above the 99th percentile reference limit but below diagnostic cutoffs for myocardial infarction.
Methods:
Electronic searches of MEDLINE, Cochrane Reviews, CINAHL and EMBASE (2002-2025) were conducted. Studies were included if outcomes for patients with indeterminate single hs-Tn measurements were reported or extractable. Patients with ECG findings suggestive of ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) were excluded. Two reviewers independently screened abstracts and extracted data. MACE was defined as acute myocardial infarction (MI), stroke, and cardiovascular mortality 30 days after index ED visit.
Results:
The search strategy yielded 709 potentially relevant citations. Eight studies were included: one randomized controlled trial, three prospective cohort, and four retrospective cohort studies. The incidence of MACE ranged from 0.3 to 14.8%. 46,066 of 129,060 eligible patients (40%) had a second test after an indeterminate result. Risk of bias was high for most observational studies, primarily due to information and incorporation bias, and randomized controlled trials had some concern for bias in the selection of the reported results, randomization process, and intended intervention.
Conclusions:
It remains unknown whether patients with an indeterminate hs-Tn result and no serial testing are at increased risk for MACE. More than half of such patients did not receive serial testing. The study demonstrates inconsistent approaches for managing indeterminate troponin results, underscoring the need for physicians to interpret indeterminate values cautiously and consider clinical assessment in low-risk chest pain patients.
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