Troponin in early presenters to rule out myocardial infarction

Abstract

Aims: Whether a single cardiac troponin measurement can safely rule out myocardial infarction in patients presenting within a few hours of symptom onset is uncertain. The study aim was to assess the performance of troponin in early presenters.

Methods and results: In patients with possible myocardial infarction, the diagnostic performance of a single measurement of high-sensitivity cardiac troponin I at presentation was evaluated and externally validated in those tested ≤3, 4-12, and >12 h from symptom onset. The limit-of-detection (2 ng/L), rule-out (5 ng/L), and sex-specific 99th centile (16 ng/L in women; 34 ng/L in men) thresholds were compared. In 41 103 consecutive patients [60 (17) years, 46% women], 12 595 (31%) presented within 3 h, and 3728 (9%) had myocardial infarction. In those presenting ≤3 h, a threshold of 2 ng/L had greater sensitivity and negative predictive value [99.4% (95% confidence interval 99.2%-99.5%) and 99.7% (99.6%-99.8%)] compared with 5 ng/L [96.5% (96.2%-96.8%) and 99.3% (99.1%-99.4%)]. In those presenting ≥3 h, the sensitivity and negative predictive value were similar for both thresholds. The sensitivity of the 99th centile was low in early and late presenters at 71.4% (70.6%-72.2%) and 92.5% (92.0%-93.0%), respectively. Findings were consistent in an external validation cohort of 7088 patients.

Conclusion: In early presenters, a single measurement of high-sensitivity cardiac troponin I below the limit of detection may facilitate the safe rule out of myocardial infarction. The 99th centile should not be used to rule out myocardial infarction at presentation even in those presenting later following symptom onset.

Trial registration: ClinicalTrials.gov NCT01852123.

Keywords: Cardiac troponin; Myocardial infarction; Symptoms.

Structured Graphical Abstract

Three panel plot showing the sensitivity (left), negative predictive value (middle) and proportion of patients (right) with cardiac troponin concentrations below 2 ng/L (red), 5 ng/L (blue), and the sex-specific 99th centile (grey) at presentation in patients presenting at or within 3 h of the onset of symptoms of myocardial infarction.

Figure 1

Consort diagram. This flow diagram shows the derivation of the study (A) and external validation (B) populations. ACS, acute coronary syndrome.

Figure 2

Performance of presentation cardiac troponin I to rule out myocardial infarction. Combined scatter and bar plot showing the sensitivity, negative predictive value, and proportion of patients with cardiac troponin concentrations below 2 ng/L, 5 ng/L, and the sex-specific 99th centile at presentation stratified by time from symptom onset, respectively. NPV, negative predictive value.

Figure 3

Impact of time on the rule out of myocardial infarction using presentation cardiac troponin I. Scatter plot with 95% confidence intervals showing the sensitivity and negative predictive value for patients with cardiac troponin concentrations at presentation below 2 ng/L, 5 ng/L, and the sex-specific 99th centile per hour from symptom onset for the diagnosis of type 1 or type 4b myocardial infarction.

Figure 4

Diagnostic performance of the limit of detection of additional cardiac troponin I assays. Combined scatter and bar plot showing the sensitivity, negative predictive value for the rule out of type 1 or 4b myocardial infarction, and proportion of patients with cardiac troponin I concentrations below the assay specific limit of detection at presentation restricted to patients undergoing troponin testing at or within 3 h of maximal symptom severity.

Figure 5

Safety of rule-out thresholds in early presenters by sub-groups. Forest plot showing negative predictive value of presentation cardiac troponin concentrations below 2 and 5 ng/L across sub-groups of patients presenting within 3 h of symptom onset. Grey horizontal line marks the target negative predictive value of 99.5%. CI, confidence interval; eGFR, estimated glomerular filtration rate.