External validation of the clinical chemistry score

BACKGROUND: Combining high-sensitivity cardiac troponin (hs-cTn) with estimated glomerular filtration rate and glucose within the Clinical Chemistry Score (CCS) could help in the assessment of patients with suspected acute myocardial infarction (AMI).

METHODS: In patients presenting with suspected AMI to the emergency department, we aimed to externally validate the performance of the CCS in a prospective international multicenter study and to directly compare the diagnostic and prognostic performance of the CCS with hs-cTnT and hs-cTnI baseline levels alone using a single cut-off approach. The diagnostic endpoint was diagnostic accuracy for AMI as centrally adjudicated by two independent cardiologists including cardiac imaging and serial hs-cTnT/I measurements. The prognostic endpoint was 30-day AMI or death.

RESULTS: AMI was the final diagnosis in 620/3827 patients (16.2%) adjudicated with hs-cTnT and 599 patients (15.7%) adjudicated with hs-cTnI. The CCS resulted in high diagnostic accuracy for AMI and prognostic accuracy for 30-days AMI/death as quantified by the area under the receiver-operating characteristic curve (AUC), using hs-cTnT 0.90 (95%CI 0.89-0.91) and 0.89 (95%CI 0.88-0.90), using hs-cTnI 0.91 (95%Cl 0.90-0.92) and 0.90 (95%CI 0.89-0.91) respectively. E.g. a CCS of 0 points resulted in a sensitivity of 99.8% (95%CI 99.1-100%) for rule-out of index AMI and 99.5% (95%CI 98.5-100%) for AMI/death at 30 days for hs-cTnT and 99.8% (95%CI 98.9-100%) and 99.6% (95%CI 98.6-100%) using hs-cTnI. Overall, the single hs-cTnT/I measurement approach provided comparable diagnostic (sensitivity 99.5-99.7%) and prognostic (sensitivity 98.9-99.5%) performance versus the CCS.

INTERPRETATION: The CCS provided high diagnostic and prognostic performance also in this independent large validation cohort. A single hs-cTnT/I measurement approach for rule-out MI yielded similar estimates.