Rising and Falling High-Sensitivity Cardiac Troponin in Diagnostic Algorithms for Patients With Suspected Myocardial Infarction

Abstract

Background High-sensitivity cardiac troponin (hs-cTn)-based diagnostic algorithms are recommended for the management of patients with suspected myocardial infarction (MI) without ST elevation. Although mirroring different phases of myocardial injury, falling and rising troponin patterns (FPs and RPs, respectively) are equally considered by most algorithms. We aimed to compare the performance of diagnostic protocols for RPs and FPs, separately. Methods and Results We pooled 2 prospective cohorts of patients with suspected MI and stratified patients to stable, FP, and RP during serial sampling separately for hs-cTnI and hs-cTnT and applied the European Society of Cardiology 0/1- and 0/3-hour algorithms comparing the positive predictive values to rule in MI. Overall, 3523 patients were included in the hs-cTnI study population. The positive predictive value for patients with an FP was significantly reduced compared with patients with an RP (0/1-hour: FP, 53.3% [95% CI, 45.0-61.4] versus RP, 76.9 [95% CI, 71.6-81.7]; 0/3-hour: FP, 56.9% [95% CI, 42.2-70.7] versus RP, 78.1% [95% CI, 74.0-81.8]). The proportion of patients in the observe zone was larger in the FP using 0/1-hour (31.3% versus 55.8%) and 0/3-hour (14.6% versus 38.6%) algorithms. Alternative cutoffs did not improve algorithm performances. Compared with stable hs-cTn, the risk for death or MI was highest in those with an FP (adjusted hazard ratio [HR], hs-cTnI 2.3 [95% CI, 1.7-3.2]; RP adjusted HR, hs-cTnI 1.8 [95% CI, 1.4-2.4]). Findings were similar for hs-cTnT tested in 3647 patients overall. Conclusions The positive predictive value to rule in MI by the European Society of Cardiology 0/1- and 0/3-hour algorithms is significantly lower in patients with FP than RP. These are at highest risk for incident death or MI. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02355457, NCT03227159.

Keywords: falling pattern; high‐sensitivity cardiac troponin; myocardial infarction; rising pattern; rule in; rule out.

Figure 1. Performance of the ESC 0/1‐hour and ESC 0/3‐hour algorithms for patients with rising or falling hs‐cTnI pattern.

Patients with stable hs‐cTnI concentrations were excluded from the algorithm analyses. No comparison was performed between the 2 algorithms, but between the rising and falling groups separately for each algorithm. ^# P<0.05 comparing the falling and rising troponin pattern groups for the provided performance parameters within an algorithm. hs‐cTn indicates high‐sensitivity cardiac troponin; MI, myocardial infarction; NPV, negative predictive value; PPV, positive predictive value; Sens, sensitivity; and Spec, specificity.

Figure 2. The positive predictive value (PPV) to rule in acute myocardial infarction using the European Society of Cardiology 0/1‐hour algorithm (left) or 0/3‐hour algorithm (right) on the basis of a high‐sensitivity cardiac troponin I assay.

Stratification has been performed by the time period of symptom onset and presentation to the emergency department. ESC indicates European Society of Cardiology.

Figure 3. Kaplan‐Meier plot for the combined end point of all‐cause death or myocardial infarction (MI) for all patients in the high‐sensitivity cardiac troponin I study population.

Patients were stratified by their troponin pattern (falling, stable, rising). Follow‐up was censored at 2 years from study enrollment. Statistical comparison was performed using the log‐rank test.