Incremental value of copeptin to highly sensitive cardiac Troponin I for rapid rule-out of myocardial infarction.
BACKGROUND
The incremental value of copeptin, a novel marker of endogenous stress, for rapid rule-out of non-ST-elevation myocardial infarction (NSTEMI) is unclear when sensitive or even high-sensitivity cardiac troponin cTn (hs-cTn) assays are used.


METHODS
In an international multicenter study we evaluated 1929 consecutive patients with symptoms suggestive of acute myocardial infarction (AMI). Measurements of copeptin, three sensitive and three hs-cTn assays were performed at presentation in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists using all clinical information including coronary angiography and levels of hs-cTnT. The incremental value in the diagnosis of NSTEMI was quantified using four outcome measures: area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI), sensitivity and negative predictive value (NPV). Early presenters (< 4h since chest pain onset) were a pre-defined subgroup.


RESULTS
NSTEMI was the adjudicated final diagnosis in 358 (18.6%) patients. As compared to the use of cTn alone, copeptin significantly increased AUC for two (33%) and IDI (between 0.010 and 0.041 (all p < 0.01)), sensitivity and NPV for all six cTn assays (100%); NPV to 96-99% when the 99 th percentile of the respective cTnI assay was combined with a copeptin level of 9 pmol/l (all p < 0.01). The incremental value in early presenters was similar to that of the overall cohort.


CONCLUSIONS
When used for rapid rule-out of NSTEM in combination with sensitive or hs-cTnI assays, copeptin provides a numerically small, but statistically and likely also clinically significant incremental value.
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Karin
K
Wildi
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Christa
C
Zellweger
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Raphael
R
Twerenbold
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Cedric
C
Jaeger
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Tobias
T
Reichlin
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Philip
P
Haaf
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Jonathan
J
Faoro
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland; Pneumology Department, Parc de Salut Mar-IMIM-UPF CIBERES (ISC iii), Barcelona, Spain; Emergency Department, Parc de Salut Mar, Barcelona, Spain.
Maria Rubini
MR
Giménez
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Andreas
A
Fischer
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Berit
B
Nelles
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Sophie
S
Druey
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Lian
L
Krivoshei
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Petra
P
Hillinger
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Christian
C
Puelacher
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Thomas
T
Herrmann
Emergency Department, Parc de Salut Mar, Barcelona, Spain.
Isabel
I
Campodarve
Laboratory Medicine, University Hospital Basel, Switzerland.
Katharina
K
Rentsch
Emergency Department, Kantonsspital Luzern, Switzerland.
Stephan
S
Steuer
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
Stefan
S
Osswald
Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland. Electronic address: chmueller@uhbs.ch.
Christian
C
Mueller
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002637:Chest Pain / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D011446:Prospective Studies; D013997:Time Factors; D019210:Troponin I / Q000097:blood*
D015415:Biomarkers; D006020:Glycopeptides; D019210:Troponin I; C048197:copeptins
Acute myocardial infarction; Copeptin; Highly sensitive Troponin I; Sensitivity and specificity