Troponin/creatine kinase ratio for discrimination of type 1 and type 2 myocardial infarction

Abstract Background High-sensitivity cardiac troponin (hs-cTn) is the laboratory gold-standard to diagnose myocardial infarction (MI). Yet, discrimination between different entities of myocardial injury, i.e. acute and chronic myocardial injury, and Type 1 (T1MI) versus Type 2 MI (T2MI), is still most challenging. Since, management of these entities is substantially different, there is an unmet clinical need for better discrimination. In clinical practice creatine-kinase (CK) is often used 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 improves the discrimination between different types of myocardial injury, and MI. Objective Our aim was to evaluate, if the combination hs-cTnI with CK improves discrimination of acute versus chronic myocardial injury, and T1MI versus T2MI. Methods We included patients presenting with suspected MI to the emergency department of a tertiary center. CK and hs-cTnI (Architect STAT) were determined at presentation, and after 1h and 3h. Final diagnoses were adjudicated according to the 4th Universal Definition of MI. STEMI patients were excluded from analyses. We calculated ratios of hs-cTnI and CK for each patient at each timepoint. Receiver-operator-curves with corresponding area under the curve (AUC) were used to assess the discriminative performance and compared with hs-cTnI alone. Logistic regression analysis was applied to calculate odds ratios (OR; 95% confidence intervals) for all ratios as well as hs-cTnI to distinguish T1MI vs T2MI, and chronic injury vs. any acute injury (acute myocardial injury, T1MI, T2MI). ORs are displayed using restricted cubic splines and values were entered log-transformed in the model. Results Of 3346 patients (median age 63 years, 36.4% women), 427 (12.8%) had MI, 103 (3.1%) had acute and 864 (25.8%) chronic injury. Log-transformed ratio of hs-cTnI/CK at presentation resulted in an AUC of 0.75 with an OR per SD for T1MI of 2.74 [2.14, 3.58], which was similar to hs-cTnI alone (AUC 0.76, p=0.75, OR per SD 3.07 [2.35, 4.09]). No significant differences were observed for measurements at 1h and 3h (Figure 1 A-C). Additionally, there was no improvement of discriminative performance regarding the discrimination of chronic and any acute myocardial injury by using hs-cTnI/CK ratios at any timepoint (AUCratio0h 0.77, AUChsTnI0h 0.8, p=0.17; ORratio0h per SD 3.44 [2.96, 4.02], ORhs-cTnI0h per SD 4.35 [3.66, 5.20]) (Fig. 1D-F). Restricted cubic splines show the overlapping correlation of increased propability for T1MI and any acute injury with higher hs-cTnI/CK ratios as well as hs-cTnI alone. (Figure 2). Conclusion The addition of CK to hs-cTnI does not improve discriminative capacity between patients with T1MI and T2MI, as well as between chronic and any acute myocardial injury compared to hs-cTnI alone.Figure 1:ROC curvesFigure 2:Natural cubic splines