Cardiac Troponin Thresholds and Kinetics to Differentiate Myocardial Injury and Myocardial Infarction

Abstract

Background: Although the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice.

Methods: In a secondary analysis of a multicenter randomized controlled trial, we identified 46 092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment-elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value and specificity were determined at the sex-specific 99th percentile upper reference limit and rule-in thresholds of 64 ng/L and 5-fold of the upper reference limit for a diagnosis of type 1 myocardial infarction.

Results: Troponin was above the 99th percentile in 8188 patients (18%). The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14% and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th-75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold upper reference limit gave a positive predictive value of 57% (95% CI, 56%-58%), 59% (58%-61%), and 62% (60%-64%) and a specificity of 96% (96%-96%), 96% (96%-96%), and 98% (97%-98%), respectively. The absolute, relative, and rate of change in troponin concentration were highest in patients with type 1 myocardial infarction (P<0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared with troponin concentration at presentation alone (area under the curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]).

Conclusions: Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01852123.

Keywords: kinetics; myocardial infarction; predictive value of tests; troponin.

Figure 1.

High-sensitivity cardiac troponin I concentrations at presentation in patients with myocardial injury and infarction. Kernel density plot of presentation troponin concentration stratified by the adjudicated diagnosis: type 1 myocardial infarction (MI; red), type 2 MI (yellow), acute myocardial injury (blue), and chronic myocardial injury (gray).

Figure 2.

Positive predictive value of high-sensitivity cardiac troponin I concentration at presentation for a diagnosis of type 1 myocardial infarction. Positive predictive value and 95% CIs of high-sensitivity cardiac troponin I concentration at presentation for type 1 myocardial infarction in all patients with suspected acute coronary syndrome (blue) and in those with a primary symptom of chest pain (red). Dotted lines illustrate the positive predictive value of the uniform 99th percentile and 5-fold upper reference limit (URL).

Figure 3.

Kinetics of high-sensitivity cardiac troponin I concentration from symptom onset in patients with myocardial injury and infarction. Spaghetti plot illustrating high-sensitivity cardiac troponin I concentrations in relation to the time of symptom onset in individual patients stratified by the adjudicated diagnosis: type 1 myocardial infarction (red), type 2 myocardial infarction (yellow), acute myocardial injury (blue), and chronic myocardial injury (gray). Plot is restricted to those patients in whom any troponin concentration was above the sex-specific 99th percentile concentration during serial testing within 12 hours of presentation and for whom the time of symptom onset was known (n=3845). Linear mixed-effects modeling was done using random intercepts and random slopes, including quadratic terms for time, with cardiac troponin I as outcome. The output from a linear mixed-effects model incorporating time from symptom onset, troponin, and change in troponin concentration is overlaid for each condition. For each condition, the final model to estimate the trajectory of cardiac troponin I was chosen according to the Akaike information criteria.

Figure 4.

Absolute and relative changes in high-sensitivity cardiac troponin I concentration on serial testing in patients with myocardial injury and infarction. Violin-density and box-and-whisker plots illustrating the absolute and relative change in high-sensitivity cardiac troponin I concentration on serial testing in patients stratified by the adjudicated diagnosis: type 1 myocardial infarction (red), type 2 myocardial infarction (yellow), acute myocardial injury (blue), and chronic myocardial injury (gray).