Derivation and validation of a novel 3hour-pathway for the observe-zone of the ESC 0/ 1h-hs-cTnI algorithm

Abstract Background The latest non-ST elevation myocardial infarction (NSTEMI) guidelines from the European Society of Cardiology (ESC) recommend a 3-hour cardiac troponin determination in patients triaged to the observe-zone of the ESC 0/1h-hs-cTnI algorithm; however, no specific cut-off for further triage is endorsed. Purpose To derive and internally validate a novel 3h-pathway for the observe-zone of the ESC 0/1h-hs-cTnI (Architect) algorithm. Methods In an multicentre international diagnostic study, we prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of MI. Final diagnoses were centrally adjudicated by two independent cardiologists applying the 4th universal definition of MI, based on complete cardiac work-up including cardiac imaging, serial hs-cTnI sampling and 90-day follow-up information. High sensitivity-cTnI (Architect) concentrations were measured at presentation and after 1 and 3 hours. The primary outcome was safety, quantified by the sensitivity and NPV for early rule out of NSTEMI. Internal validation was assessed with a bootstrapping procedure. Results Among 2481 eligible patients, application of the ESC 0/1h-algorithm triaged 1725 patients (69.5%) to either rule-out or rule-in of NSTEMI, remaining 756 patients (30.5%) in the observe-zone (adjudicated NSTEMI prevalence 65/756 patients, 13.7%). A novel derived 3h-pathway for the observe-zone patients ruled-out NSTEMI with a 3h hs-cTnI concentration <8 ng/L and a 0/3h-hs-cTnI absolute change <3 ng/L, triaging 241 patients (32%) towards rule-out, resulting in a sensitivity of 100% (95%CI 94.4-100) and a NPV of 100% (95%CI 98.4-100). A 0/3h-hs-cTnI absolute change ≥8 ng/L ruled-in 69 patients (9.1%), resulting in a specificity of 95.8% (95%CI 94.0-97.1) and a PPV of 58.0% (95%CI 46.2-68.9), Figure. The novel 3h-pathway reduced the number of patients remaining in the observe zone from 756 (30.5%) to 446 (18%), resulting in a relative reduction of 41%, while the number of NSTEMI was reduced from 65 to 25, resulting in a relative reduction of 62%. Findings were confirmed in the optimism-corrected bootstrap internal validation. Conclusions A novel derived pathway combining a 3h hs-cTnI concentration <8 ng/L and a 0/3h absolute change <3 ng/L allowed to safely rule-out NSTEMI in patients remaining in the observe-zone of the ESC 0/1h-hs-cTnI (Architect) algorithm.Performance of the novel derived cutoffs