Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction

Author:

van der Linden Noreen1,Wildi Karin2,Twerenbold Raphael2,Pickering John W.3,Than Martin3,Cullen Louise456,Greenslade Jaimi56,Parsonage William456,Nestelberger Thomas2,Boeddinghaus Jasper2,Badertscher Patrick2,Rubini Giménez Maria27,Klinkenberg Lieke J.J.1,Bekers Otto1,Schöni Aline28,Keller Dagmar I.8,Sabti Zaid2,Puelacher Christian2,Cupa Janosch2,Schumacher Lukas2,Kozhuharov Nikola2,Grimm Karin2,Shrestha Samyut2,Flores Dayana2,Freese Michael2,Stelzig Claudia2,Strebel Ivo2,Miró Òscar9,Rentsch Katharina10,Morawiec Beata11,Kawecki Damian11,Kloos Wanda212,Lohrmann Jens2,Richards A. Mark3,Troughton Richard3,Pemberton Christopher3,Osswald Stefan2,van Dieijen-Visser Marja P.1,Mingels Alma M.1,Reichlin Tobias2,Meex Steven J.R.1,Mueller Christian2

Affiliation:

1. Department of Clinical Chemistry, Central Diagnostic Laboratory, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC), The Netherlands (N.v.d.L., L.J.J.K., O.B., M.P.v.D.-V., A.M.M., S.J.R.M.)

2. Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland (K.W., R.T., T.N., J.B., P.B., M.R.G., A.S., Z.S., C.P., J.C., L.S., N.K., K.G., S.S., D.F., M.F., C.S., I.S., W.K., J.L., S.O., T.R., C.M.)

3. Department of Medicine, University of Otago, Christchurch, New Zealand (J.W.P., M.T., A.M.R., R.T., C.P.)

4. Department of Emergency Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Australia (L.C., W.P.)

5. School of Public Health, Queensland University of Technology, Brisbane, Australia (L.C., J.G., W.P.)

6. School of Medicine, The University of Queensland, Brisbane, Australia (L.C., J.G., W.P.)

7. Emergency Department, CIBERES ISC III, Hospital del Mar – IMIM, Barcelona, Spain (M.R.)

8. Emergency Department, University Hospital Zürich, Switzerland (A.S., D.I.K.)

9. Emergency Department, Hospital Clinic, Barcelona, Spain (O.M.)

10. Laboratory Medicine, University Hospital Basel, Switzerland (K.R.)

11. 2nd Department of Cardiology and School of Medicine with the Division of Dentistry, Zabrze, Medical University of Katowice, Katowice, Poland (B.M., D.K.).

12. Critical Care Research Group, The Prince Charles Hospital, Brisbane, Australia (K.W.)

Abstract

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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