Combining High Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction.
Circulation. 2018 Apr 24;:
Authors: van der Linden N, Wildi K, Twerenbold R, Pickering JW, Than M, Cullen L, Greenslade J, Parsonage W, Nestelberger T, Boeddinghaus J, Badertscher P, Rubini Giménez M, Klinkenberg LJJ, Bekers O, Schöni A, Keller DI, Sabti Z, Puelacher C, Cupa J, Schumacher L, Kozhuharov N, Grimm K, Shrestha S, Flores D, Freese M, Stelzig C, Strebel I, Miró Ò, Rentsch K, Morawiec B, Kawecki D, Kloos W, Lohrmann J, Richards AM, Troughton R, Pemberton C, Osswald S, van Dieijen-Visser MP, Mingels AM, Reichlin T, Meex SJR, Mueller C
Background -Combining two 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 (AMI) 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 AMI. 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 AMI. 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 ESC 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 ESC 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule out criteria after the baseline blood sampling was limited (6-24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng2/L2) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34-41% in the original (sum: negative predictive value (NPV) 100% (95%CI: 99.5-100%); product: NPV 100% (95%CI: 99.5-100%) 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 (40-43% 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 (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 AMI. Clinical Trial Registration -APACE URL: www.clinicaltrial.gov, Unique Identifier: NCT00470587; ADAPT URL: www.anzctr.org.au, Unique Identifier: ACTRN12611001069943.
PMID: 29691270 [PubMed - as supplied by publisher]