Aims This study tested the hypothesis that combining stress-induced biomarkers (copeptin or glucose) with high-sensitivity cardiac troponin (hs-cTn) increases diagnostic accuracy for non-ST-elevation myocardial infarction (NSTEMI) in patients presenting to the emergency department. Methods and results The ability to rule-out NSTEMI for combinations of baseline hs-cTnT or hs-cTnI with copeptin or glucose was compared with the European Society of Cardiology (ESC) hs-cTnT/I-only rule-out algorithms in two independent (one Norwegian and one international multicentre) diagnostic studies. Among 959 patients (median age 64 years, 60.5% male) with suspected NSTEMI in the Norwegian cohort, 13% had NSTEMI. Adding copeptin or glucose to hs-cTnT/I as a continuous variable did not improve discrimination as quantified by the area under the curve {e.g. hs-cTnT/copeptin 0.91 [95% confidence interval (CI) 0.89–0.93] vs. hs-cTnT alone 0.91 (95% CI 0.89–0.93); hs-cTnI/copeptin 0.85 (95% CI 0.82–0.87) vs. hs-cTnI alone 0.93 (95% CI 0.91–0.95)}, nor did adding copeptin <9 mmol/L or glucose <5.6 mmol/L increase the sensitivity of the rule-out provided by hs-cTnT <5 ng/L or hs-cTnI <4 ng/L in patients presenting more than 3 h after chest pain onset (target population in the ESC-0 h-algorithm). The combination decreased rule-out efficacy significantly (both P < 0.01). These findings were confirmed among 1272 patients (median age 62 years, 69.3% male) with suspected NSTEMI in the international validation cohort, of which 20.7% had NSTEMI. A trend towards increased sensitivity for the hs-cTnT/I/copeptin combinations (97–100% vs. 91–97% for the ESC-0 h-rule-out cut-offs) was observed in the Norwegian cohort. Conclusion Adding copeptin or glucose to hs-cTnT/I did not increase diagnostic performance when compared with current ESC guideline hs-cTnT/I-only 0 h-algorithms.

Background The accuracy for early identification of non-ST-elevation myocardial infarction (NSTEMI) in the emergency department must be determined for all novel high-sensitivity cardiac troponin assays (hs-cTn). In this prospective, multi-centre study we developed rule-out algorithms for a high-sensitivity cardiac troponin I (hs-cTnI) assay and compared it to established algorithms for hs-cTnT and hs-cTnI. Methods Two rule-out algorithms for NSTEMI were developed from a derivation cohort of 977 patients assessed by the Siemens Atellica IM hs-cTnI assay. Diagnostic performance was compared with hs-cTnT (Roche) and hs-cTnI (Abbott) algorithms. The derived algorithms were tested in two different validation cohorts (n=518 and n=405, respectively). Results An admission sample algorithm (hs-cTnI (Siemens)) for rule-out of NSTEMI with cutoff <5 ng/L had negative predictive value (NPV) 99.4–100.0%, sensitivity 98.3–100% and specificity 46.7–56.5% in the two validation cohorts. Sensitivity and NPV was similar, specificity trended towards improvement over the comparator algorithms (Figure 1). A 0–1 hour algorithm (hs-cTnI (Siemens)) with cutoff <10 ng/L and Δ change <3 ng/L achieved sensitivity and NPV 100% with specificity >70% in both validation cohorts, similar to the comparator algorithms (Table 1). Conclusions Rule-out algorithms from the Siemens Atellica hs-cTnI assay has comparable diagnostic accuracy to established hs-cTn rule-out algorithms. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Public grant: Western Norway Regional Health Authority.Private company funding: Siemens Healthineers AG

Background NSTEMI may be ruled out in patients presenting with acute chest pain based on low baseline high sensitivity troponin (cTn) at admission. This procedure is limited by a low expected frequency of ruled out non-cardiac chest pain (NCCP) patients. Purpose To investigate if stress-induced biomarkers (glucose or copeptin) combined with cTn can increase the rate of NCCP ruled out without an unacceptable increase in incorrectly ruled out NSTEMI. Method 971 patients with suspected NSTE-ACS were included. Final diagnosis was adjudicated by two independent cardiologists using clinical data including routine cTnT. Additionally, baseline cTnI, cTnI from Singulex Clarity System (cTnI(sgx)), copeptin and glucose were measured. Diagnostic performance to rule out NSTEMI was compared between the ESC rule out algorithms for cTnT and cTnI(Abbott), a local cTnI(sgx) algorithm and different combinations of cTn with copeptin or glucose Results Median age 61 years, 60% male. 13% had NSTEMI, 12% had UAP and 60% NCCP. Distribution of copeptin and glucose concentrations (NSTEMI and NCCP) is shown in figure 1. Copeptin and cTnT produces an algorithm with lower miss rate for NSTEMI, increased rule out rate for NCCP and significantly higher AUC (DeLong test, p value <0.001) compared to the ESC algorithm (Table 1). cTnI(sgx) and copeptin showed higher rule out for NCCP and higher AUC (p value <0.001), however an increased rule out rate for NSTEMIs. Combining cTnI(Abbott) and glucose gave a similar miss rate for NSTEMI as ESC, but increased rule out rate for NCCP and higher AUC (p value <0.001). Conclusion Combining cTnT or cTnI(sgx) with copeptin; or cTnI with glucose, improves diagnostic precision and efficacy of rule out protocols for NSTEMI in patients presenting with acute chest pain. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Western Norway Regional Health Authority; Haukeland and Stavanger University Hospitals