Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction
Authors: van der Linden Noreen , Wildi Karin , Twerenbold Raphael , Pickering John W. , Than Martin , Cullen Louise , Greenslade Jaimi , Parsonage William , Nestelberger Thomas , Boeddinghaus Jasper , Badertscher Patrick , Rubini Giménez Maria , Klinkenberg Lieke J.J. , Bekers Otto , Schöni Aline , Keller Dagmar I. , Sabti Zaid , Puelacher Christian , Cupa Janosch , Schumacher Lukas , Kozhuharov Nikola , Grimm Karin , Shrestha Samyut , Flores Dayana , Freese Michael , Stelzig Claudia , Strebel Ivo , Miró Òscar , Rentsch Katharina , Morawiec Beata , Kawecki Damian , Kloos Wanda , Lohrmann Jens , Richards A. Mark , Troughton Richard , Pemberton Christopher , Osswald Stefan , van Dieijen-Visser Marja P. , Mingels Alma M. , Reichlin Tobias , Meex Steven J.R. , Mueller Christian 
Published: April 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 <4 ng/L and hs-cTnT <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.