External validation of a diagnostic stepwise 0/1/3h algorithm for patients with suspected myocardial infarction

Background: Application of the 0/1h-algorithm is the guideline-recommended approach in patients with suspected myocardial infarction (MI) for rapid diagnosis or rule-out. Despite good diagnostic performance, a significant proportion of patients remain in the observe group after 1h in need for further diagnostic measures. Recently, specific cutoffs for hs-TnT at three hours have been proposed, enabling an additional serial triage option.

Objective: Our aim was to externally validate the diagnostic performance of the 0/1/3h algorithm in patients with suspected MI.

Methods: Patients with symptoms suggestive of MI were consecutively enrolled in the emergency department of a German tertiary hospital. We excluded patients with ST-elevation MI. Serial measurements of hs-TnT were performed at presentation, after 1h and 3h. Final diagnoses, as defined by the 4th Universal Definition of MI, were adjudicated independently by two cardiologists. Patients were categorized into rule-in, rule-out- and observe-group, applying the 0/1/3h-algorithm. Diagnostic performance parameters were assessed in the overall study population as well as for predefined subgroups including sex, age, glomerular filtration rate (GFR), and symptom onset time.

Results: In 2,514 patients (median age 64 years, 36.4% females), MI prevalence was 14.4%. Application of the 0/1/3h algorithm ruled-out 1511 (60.1%) and ruled-in 587 (23.3%) patients with only 416 (16.6%) remaining in the observe group at 3h as compared to 689 (27.4%) at 1h. We observed high rule-out safety with a sensitivity of 98.6% (95%CI 96.8%, 99.4%) and a corresponding negative predictive value of 99.7% (95%CI 99.2%, 99.9%). Rule-in performance was acceptable with a specificity of 89.3% (95%CI 87.9%, 90.5%) and positive predictive value of 60.8% (95%CI 56.8, 64.7, Figure 1). In predefined subgroup analyses, safety of rule-out was marginally but statistically lower in patients with normal as compared with impaired renal function (p both <0.001). Further, specificity of rule-in was substantially lower in older patients aged ≥ 65 years (84.8% vs. 93.3%, p<0.001), patients with GFR<60ml/min/1.73m² (78.3% vs. 93.0%, p<0.001) as well as in male patients (88.1% vs. 91.2%, p=0.028) (Figure 2).  The proportion of patients remaining in the observe group after 3h was significantly higher in patients with impaired renal function (32.3% vs. 10.9%), as well as in elderly patients ≥ 65 years (26.8% vs. 6.8%).

Conclusion: Application of the 0/1/3h algorithm in patients with suspected MI resulted in good diagnostic performance with high rule-out safety and moderate rule-in capacity. In patients with impaired renal function as well as elderly patients, specificity of rule-in was significantly reduced and proportion of patients remaining in the observe zone at three hours was increased.