Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction
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Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction. / 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.
In: CIRCULATION, Vol. 138, No. 10, 04.09.2018, p. 989-999.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 - Rubini Giménez, Maria
AU - Klinkenberg, Lieke J J
AU - Bekers, Otto
AU - Schöni, 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 - Miró, Òscar
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 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% 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 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% 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 - Australia
KW - Biomarkers/blood
KW - Early Diagnosis
KW - Europe
KW - Humans
KW - Myocardial Infarction/blood
KW - New Zealand
KW - Predictive Value of Tests
KW - Prospective Studies
KW - Reproducibility of Results
KW - Time Factors
KW - Troponin I/blood
KW - Troponin T/blood
KW - Up-Regulation
U2 - 10.1161/CIRCULATIONAHA.117.032003
DO - 10.1161/CIRCULATIONAHA.117.032003
M3 - SCORING: Journal article
C2 - 29691270
VL - 138
SP - 989
EP - 999
JO - CIRCULATION
JF - CIRCULATION
SN - 0009-7322
IS - 10
ER -