TY - JOUR
T1 - Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction
AU - van der Linden, Noreen
AU - Wildi, Karin
AU - Twerenbold, Raphael
AU - Pickering, John W.
AU - Than, Martin
AU - Cullen, Louise
AU - Greenslade, Jaimi
AU - Parsonage, William
AU - Nestelberger, Thomas
AU - Boeddinghaus, Jasper
AU - Badertscher, Patrick
AU - Gimenez, Maria
AU - Klinkenberg, Lieke J. J.
AU - Bekers, Otto
AU - Schoni, Aline
AU - Keller, Dagmar I.
AU - Sabti, Zaid
AU - Puelacher, Christian
AU - Cupa, Janosch
AU - Schumacher, Lukas
AU - Kozhuharov, Nikola
AU - Grimm, Karin
AU - Shrestha, Samyut
AU - Flores, Dayana
AU - Freese, Michael
AU - Stelzig, Claudia
AU - Strebel, Ivo
AU - Miro, Oscar
AU - Rentsch, Katharina
AU - Morawiec, Beata
AU - Kawecki, Damian
AU - Kloos, Wanda
AU - Lohrmann, Jens
AU - Richards, A. Mark
AU - Troughton, Richard
AU - Pemberton, Christopher
AU - Osswald, Stefan
AU - van Dieijen-Visser, Marja P.
AU - Mingels, Alma M.
AU - Reichlin, Tobias
AU - Meex, Steven J. R.
AU - Mueller, Christian
PY - 2018/9/4
Y1 - 2018/9/4
N2 - 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.
AB - 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.
KW - combination
KW - diagnosis
KW - myocardial infarction
KW - troponins
KW - GLOMERULAR-FILTRATION-RATE
KW - ACUTE CORONARY SYNDROMES
KW - SOCIETY-OF-CARDIOLOGY
KW - ACID-BINDING PROTEIN
KW - CHEST-PAIN
KW - EMERGENCY-DEPARTMENT
KW - RULE-OUT
KW - RISK STRATIFICATION
KW - RAPID RULE
KW - COLLABORATIVE METAANALYSIS
U2 - 10.1161/CIRCULATIONAHA.117.032003
DO - 10.1161/CIRCULATIONAHA.117.032003
M3 - Article
C2 - 29691270
SN - 0009-7322
VL - 138
SP - 989
EP - 999
JO - Circulation
JF - Circulation
IS - 10
ER -