External validation of the clinical chemistry score

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).

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.

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.

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.