Purpose: Addressing the increasingly recognized, yet unmet clinical need for rapid rule-out of acute myocardial infarction (AMI), several novel strategies have been developed. Due to the lack of direct comparisons in the same dataset, selection of the best strategy for clinical practice is challenging. We therefore aimed to directly compare the safety and efficacy of two previously defined strategies: 2h Accelerated Diagnostic Protocol (ADP) versus the hs-cTn 2h-algorithm).

Methods: In a prospective international multicentre diagnostic study enrolling 1814 patients presenting with suspected AMI to the emergency department, the final diagnosis of AMI was adjudicated by two independent cardiologists using all available clinical information including serial hs-cTnT concentrations. Safety was quantified as the negative predictive value for AMI in the rule-out zone of the respective rule-out strategies. Efficacy was quantified as the percentage of the overall cohort assigned to the rule-out zone by the respective strategy. The 2h-algorithm rule-out was defined as 0h and 2h levels<14ng/l and Δ0–2h<4ng/l; and 2h ADP rule-out was defined as 0h and 2h Levels≤14ng/l, no significant ECG changes and TIMI Score ≤1. As both strategies should only be applied once ST-elevation MI (STEMI) has been excluded by the initial ECG, STEMI patients were excluded from the analysis.

Results: Acute myocardial infarction was the final diagnosis in 16% of patients. Using hs-cTnT, the safety was very high and comparable with both algorithms (2h-ADP: NPV 100%, 95% CI 99.5–100% versus 2h-algorithm: NPV 99.9%, 95% CI 99.5–100% p=ns). Regarding efficacy, 2h ADP allowed rule-out in 38% of patients versus 64% with the 2h-algorithm (p<0.001).

Conclusion: Both investigated rule-out strategies allow a safe rule-out of AMI. However the 2h algorithm has a much higher efficacy compared to 2h ADP, allowing the rule-out of the double of patients and without the need of the TIMI Score calculation.