Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction
Authors: Noreen van der Linden, Karin Wildi, Raphael Twerenbold, John W. Pickering, Martin Than, Louise Cullen, Jaimi Greenslade, William Parsonage, Thomas Nestelberger, Jasper Boeddinghaus, Patrick Badertscher, Maria Rubini Giménez, Lieke J.J. Klinkenberg, Otto Bekers, Aline Schöni, Dagmar I. Keller, Zaid Sabti, Christian Puelacher, Janosch Cupa, Lukas Schumacher, Nikola Kozhuharov, Karin Grimm, Samyut Shrestha, Dayana Flores, Michael Freese, Claudia Stelzig, Ivo Strebel, Òscar Miró, Katharina Rentsch, Beata Morawiec, Damian Kawecki, Wanda Kloos, Jens Lohrmann, A. Mark Richards, Richard Troughton, Christopher Pemberton, Stefan Osswald, Marja P. van Dieijen-Visser, Alma M. Mingels, Tobias Reichlin, Steven J.R. Meex, Christian Mueller
Journal: Circulation (2018)

Background: Combining 2 signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some individual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high-sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of acute myocardial infarction. Methods: The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio, and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected acute myocardial infarction. The optimal rule-out and rule-in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule-out was compared with the European Society of Cardiology 0/1 and 0/3 hour algorithms. Results: Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the individual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the European Society of Cardiology 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule-out criteria after the baseline blood sampling was limited (6% to 24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng 2 /L 2 ) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34% to 41% in the original (sum: negative predictive value [NPV] 100% [95% confidence interval (CI), 99.5% to 100%]; product: NPV 100% [95% CI, 99.5% to 100%]) and in the validation cohort (sum: NPV 99.6% [95% CI, 99.0–99.9%]; product: NPV 99.4% [95% CI, 98.8–99.8%]). The use of a combination algorithm (hs-cTnI &lt;4 ng/L and hs-cTnT &lt;9 ng/L) showed comparable results for rule-out (40% to 43% ruled out; NPV original cohort 99.9% [95% CI, 99.2–100%]; NPV validation cohort 99.5% [95% CI, 98.9–99.8%]) and rule-in (positive predictive value [PPV] original cohort 74.4% [95% Cl, 69.6–78.8%]; PPV validation cohort 84.0% [95% Cl, 79.7–87.6%]). Conclusions: New strategies combining hs-cTnI and hs-cTnT concentrations may significantly increase the number of patients eligible for very early and safe rule-out, but do not seem helpful for the rule-in of acute myocardial infarction. Clinical Trial Registration: URL (APACE): https://www.clinicaltrial.gov . Unique identifier: NCT00470587. URL (ADAPT): www.anzctr.org.au . Unique identifier: ACTRN12611001069943.