Combining High Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction
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
- High-sensitivity cardiac troponin
- combination of assays for diagnosis
- early rule-out
- early rule-in
- acute myocardial infarction
- Received October 1, 2017.
- Revision received March 20, 2018.
- Accepted April 10, 2018.