Troponin T/creatine kinase ratio for discrimination of different entities of myocardial injury

Background: High-sensitivity cardiac troponin (hs-cTn) is the laboratory gold-standard in the diagnostic workup of suspected myocardial infarction (MI). Despite excellent diagnostic performance of existing algorithms to identify MI, discrimination between Type 1 (T1MI) and Type 2 MI (T2MI) is still challenging. Creatine-kinase (CK) is frequently used in clinical practice to decide whether patients with elevated hs-cTn concentrations are referred to primary invasive coronary angiography. However, it is unclear if the combined evaluation of CK and hs-cTn potentially improves the discrimination between different types of myocardial injury, and MI.

Objective: To evaluate, if addition of CK concentrations to hs-cTnT improve the discrimination between different MI subtypes as well as between acute and chronic myocardial injury.

Methods: Patients presenting with symptoms suggestive of MI to the emergency department of a tertiary center in Germany were consecutively enrolled. Concentrations of hs-cTnT and CK were serially measured at presentation, after 1h and 3h. Ratios of hs-cTnT and CK were calculated for each patient at each timepoint. Adjudication of final diagnoses was performed according to the 4th Universal Definition of MI by two physicians. We plotted Receiver-operator-curves with corresponding area under the curve (AUC) assessing the discriminative capacity of the hs-cTnT/CK ratios compared with hs-cTnT alone. Further, logistic regression analysis were performed to calculate odds ratios (OR) for all ratios as well as for hs-cTnT alone to distinguish T1MI vs T2MI, any acute injury (acute myocardial injury, T1MI, T2MI) versus chronic injury and T1MI vs. other acute injury (acute myocardial injury, T2MI).

Results:  In total, of 3,346 patients (median age 63 years, 36.4% women), 427 (12.8%) had any MI, 281 T1MI and 146 T2MI, 103 (3.1%) acute and 864 (25.8%) chronic myocardial injury. For the discrimination of T1MI versus T2MI, log-transformed ratio of hs-cTnT/CK at presentation resulted in an AUC of 0.71 with an OR per SD for T1MI of 2.13 (95%CI 1.69, 2.71), similar to hs-cTnT alone (AUC 0.72, p for comparison=0.61, OR per SD 2.46 [1.93, 3.19]) (Figure 1). No relevant differences were observed for ratios at 1h and 3h. Also, there was no improvement in discriminate capacity regarding the discrimination of chronic- and any acute myocardial injury (AUC_ratio0h 0.69, AUC_hs-cTnT0h 0.75, p for comparison=0.007; OR_ratio0h per SD 2.10 [1.85, 2.38], OR_hs-cTnT0h per SD 3.24 [2.80, 3.79]) nor T1MI and other acute myocardial injury (AUC_ratio0h 0.61, AUC_hs-cTnT0h 0.64, p for comparison=0.32; OR_ratio0h per SD 1.44 [1.21, 1.73], OR_hs-cTnT0h per SD 1.67 [1.39, 2.02]) by using hs-cTnT/CK ratios at any timepoint (Figure 1). Restricted cubic splines show the overlapping correlation of increased probability for T1MI vs. T2MI, any acute injury vs. chronic injury and T1MI vs. other acute injury with higher hs-cTnT/CK ratios as well as for increasing hs-cTnT concentrations alone. (Figure 2).

Conclusion: The combined interpretation of CK and hs-cTnT as a ratio does not improve discrimination between patients with T1MI and T2MI, between chronic and any acute myocardial injury as well as between T1MI and other acute myocardial injury compared to hs-cTnT alone.