Novel Criteria for the Observe-Zone of the ESC 0/1h-hs-cTnT Algorithm
Authors: Lopez-Ayala Pedro , Nestelberger Thomas , Boeddinghaus Jasper , Koechlin Luca , Ratmann Paul David , Strebel Ivo , Gehrke Juliane , Meier Severin , Walter Joan , Rubini Gimenez Maria , Mutschler Eugenio , Miró Òscar , López-Barbeito Beatriz , Martín-Sánchez Francisco Javier , Rodríguez-Adrada Esther , Keller Dagmar I. , Newby L. Kristin , Twerenbold Raphael , Giannitsis Evangelos , Lindahl Bertil , Mueller Christian , Zimmermann Tobias , Schoepfer Hadrien , Coscia Tania , Troester Valentina , Reichlin Tobias , Kaeslin Marina , Christ Michael , Meier Mario , Badertscher Patrick , Puelacher Christian , du Fay de Lavallaz Jeanne , Potlukova Eliska , Kawecki Damian , Geigy Nicolas , Rentsch Katharina , Shrestha Samyut , Morawiec Beata , Munzk Piotr , Breidthardt Tobias , Freese Michael , Martinez-Nadal Gemma , Fuenzalida Carolina , Calderón Sofia , Rodriguez Adrada Esther , Ganovská Eva , Parenica Jiri , von Eckardstein Arnold , Campodarve Isabel , Gea Joachim , Mccord James , Nowak Richard , Body Richard , deFilippi Christopher R. , Christenson Robert H. , Panteghini Mauro , Plebani Mario , Verschuren Franck , French John , Weiser Silvia , Jernberg Tomas 
Published: August 2021

Background:
The non–ST-segment–elevation myocardial infarction (NSTEMI) guidelines of the European Society of Cardiology (ESC) recommend a 3h cardiac troponin determination in patients triaged to the observe-zone of the ESC 0/1h-algorithm; however, no specific cutoff for further triage is endorsed. Recently, a specific cutoff for 0/3h high-sensitivity cardiac troponin T (hs-cTnT) change (7 ng/L) was proposed, warranting external validation.

Methods:
Patients presenting with acute chest discomfort to the emergency department were prospectively enrolled into an international multicenter diagnostic study. Final diagnoses were centrally adjudicated by 2 independent cardiologists applying the fourth universal definition of myocardial infarction, on the basis of complete cardiac workup, cardiac imaging, and serial hs-cTnT. Hs-cTnT concentrations were measured at presentation, after 1 hour, and after 3 hours. The objective was to externally validate the proposed cutoff, and if necessary, derive and internally as well as externally validate novel 0/3h-criteria for the observe-zone of the ESC 0/1h-hs-cTnT-algorithm in an independent multicenter cohort.

Results:
Among 2076 eligible patients, application of the ESC 0/1h-hs-cTnT-algorithm triaged 1512 patients (72.8%) to either rule out or rule in NSTEMI, leaving 564 patients (27.2%) in the observe-zone (adjudicated NSTEMI prevalence, 120/564 patients, 21.3%). The suggested 0/3h-hs-cTnT-change of <7 ng/L triaged 517 patients (91.7%) toward rule-out, resulting in a sensitivity of 33.3% (95% CI, 25.5–42.2), missing 80 patients with NSTEMI, and ≥7 ng/L triaged 47 patients toward rule-in (8.3%), resulting in a specificity of 98.4% (95% CI, 96.8–99.2). Novel derived 0/3h-criteria for the observe-zone patients ruled out NSTEMI with a 3h hs-cTnT concentration <15 ng/L and a 0/3h-hs-cTnT absolute change <4 ng/L, triaging 138 patients (25%) toward rule-out, resulting in a sensitivity of 99.2% (95% CI, 96.0–99.9), missing 1 patient with NSTEMI. A 0/3h-hs-cTnT absolute change ≥6 ng/L triaged 63 patients (11.2%) toward rule-in, resulting in a specificity of 98% (95% CI, 96.2–98.9) Thereby, the novel 0/3h-criteria reduced the number of patients in the observe zone by 36%s and the number of type 1 myocardial infarction by 50%. Findings were confirmed in both internal and external validation.

Conclusions:
A combination of a 3h-hs-cTnT concentration (<15 ng/L) and a 0/3h absolute change (<4 ng/L) is necessary to safely rule out NSTEMI in patients remaining in the observe-zone of the ESC 0/1h-hs-cTnT-algorithm.

Registration:

URL:
https://clinicaltrials.gov
; Unique identifier: NCT00470587.