Utilizing the European Society of Cardiology 0/3-h algorithm to triage the 0/1-h algorithm observe-zone

The development of high-sensitivity cardiac troponin (hs-cTn) has accelerated the diagnosis of acute myocardial infarction (AMI). Among various hs-cTn-based diagnostic protocols, the European Society of Cardiology (ESC) 0/1-h algorithm has high diagnostic accuracy but leaves ∼25–30% of patients in the observe-zone.1 Two studies have derived novel criteria for the observe-zone2,3; nevertheless, diagnostic performances of these criteria were suboptimal. In the latest ESC guidelines, the 0/3-h algorithm is recommended as an alternative strategy to the 0/1-h and 0/2-h algorithms. In contrast to the 0/1- and 0/2-h algorithms that use specific hs-cTn thresholds, the 0/3-h algorithm utilizes the 99th percentile upper reference limit (URL) of a normal reference population as thresholds to triage AMI. When combined with clinical risk scores, the 0/3-h algorithm has a high sensitivity that approximates the 99% safety benchmark.1 In this study, we combined the 99th percentile URL threshold with various clinical risk scores to stratify patients in the observe-zone. We performed a secondary analysis of a prospective cohort study, which has been approved by the ethics committee (certificate Si 328/2017).4 We included Thai adults aged >25 years presenting with symptoms suggestive of AMI with an onset of <24 h. The main exclusion criteria were ST-elevation myocardial infarction (MI) and recent coronary interventions. Patients were triaged into rule-out, observe, or rule-in according to the ESC 0/1-h algorithm using the 5th generation Roche high-sensitivity cardiac troponin T (hs-cTnT) assay. A third hs-cTnT testing was ordered at 3 h for patients in the observe-zone. In the 0/3-h cardiac troponin-only protocol, patients were eligible for rule-out if they had a 0/3-h change in hs-cTnT <7 ng/L (50% of 99th percentile URL) when the initial hs-cTnT was ≤14 ng/L (99th percentile URL), or if they had a 0/3-h change in hs-cTnT <20% of the initial hs-cTnT when the initial hs-cTnT was >14 ng/L (99th percentile URL).5 We combined the 0/3-h protocol with the following clinical risk scores: Global Registry of Acute Coronary Events (GRACE), History, ECG, Age, Risk Factors and Troponin (HEART), Thrombolysis in Myocardial Infarction (TIMI), and Troponin-only Manchester Acute Coronary Syndromes (T-MACS). The primary outcome was index AMI. The diagnosis was independently adjudicated by two senior emergency physicians using the Third Universal Definition of MI. We calculated diagnostic accuracy as sensitivity, negative predictive value (NPV), specificity, positive predictive value (PPV), and efficacy as the proportion of patients triaged towards rule-out or rule-in. Among 350 participants, 128 (36.6%) patients were placed in the observe-zone. The 0/3-h cardiac troponin-only algorithm ruled out 116 (91%) patients, with five cases of missed non-ST elevation myocardial infarction (NSTEMI), resulting in a sensitivity and NPV of 61.5% [95% confidence interval (CI): 31.6–81.1] and 96.5% (95% CI: 91.3–99.0) (Table 1). Using the complete ESC 0/3-h algorithm by incorporating GRACE score <140 ruled out 52 (41%) patients, with 1 case of missed NSTEMI, resulting in a sensitivity and NPV of 92.3% (95% CI: 64.0–99.8) and 98.1% (95% CI: 88.6–99.7). When combined with other clinical scores, the 0/3-h algorithm did not miss any NSTEMI, but only ruled out 20% or less of the patients. The 0/3-h cardiac troponin-only algorithm ruled in 12 (9%) patients, with a specificity and PPV of 96.5% (95% CI: 91.3–99.0) and 66.3% (95% CI: 40.7–84.9). Adding GRACE score >140 to the 0/3-h algorithm ruled in 7 (5%) patients, with a specificity and PPV of 96.5% (95% CI: 91.3–99.0) and 42.4% (95% CI: 15.6–74.6). The 0/3-h algorithm had comparable rule-in specificity and PPV across other clinical risk scores. In comparison with the complete ESC 0/3-h algorithm, the Parkland criteria2 ruled out more patients (41% vs. 92%) but with a significantly lower sensitivity [92.3% (95% CI: 64.0–99.8) vs. 46.2% (95% CI: 19.2–74.9)]. The Advantageous Predictors of Acute Coronary Syndromes Evaluation (APACE) criteria3 ruled out fewer patients (41% vs. 13%) with similar sensitivity [both 92.3% (95% CI: 64.0–99.8)]. Diagnostic performance of different criteria for triaging patients in the observe-zone APACE, Advantageous Predictors of Acute Coronary Syndromes Evaluation; CI, confidence interval; ESC, European Society of Cardiology; GRACE, Global Registry of Acute Coronary Events; HEART, History, Electrocardiogram, Age, Risk Factors, Troponin; hs-cTnT, high-sensitivity cardiac troponin T; NPV, negative predictive value; PPV, positive predictive value; T-MACS, Troponin-only Manchester Acute Coronary Syndromes; TIMI, Thrombolysis In Myocardial Infarction; URL, upper reference limit. Patients were ruled out if they had a 0/3-h change in hs-cTnT <7 ng/L (50% of 99th percentile URL) when the initial hs-cTnT was ≤14 ng/L (99th percentile URL), or if they had a 0/3-h change in hs-cTnT <20% of the initial hs-cTnT when the initial hs-cTnT was >14 ng/L (99th percentile URL). The pain-free criterion required for rule-out as stipulated in the ESC guidelines was not included. Patients were ruled in if they had a 0/3-h change in hs-cTnT ≥7 ng/L (50% of 99th percentile URL) when the initial hs-cTnT was ≤14 ng/L (99th percentile URL), or if they had a 0/3-h change in hs-cTnT ≥20% of the initial hs-cTnT when the initial hs-cTnT was >14 ng/L (99th percentile URL). Patients were ruled out if they had a 0/3-h change in hs-cTnT <7 ng/L. Patients were ruled in if they had a 0/3-h change in hs-cTnT ≥7 ng/L. Patients were ruled out if they had a 3-h hs-cTnT <15 ng/L and 0/3-h change in hs-cTnT <4 ng/L. Patients were ruled in if they had a 0/3-h change in hs-cTnT ≥6 ng/L. Our findings suggest that the ESC 0/3-h algorithm (incorporating GRACE score <140) may provide the most optimal balance between safety and efficacy in triaging patients in the observe-zone compared with the Parkland and APACE criteria. First, close to 50% of patients in the observe-zone could be triaged at very high sensitivity (92.3%) and specificity (96.5%). By contrast, the Parkland criteria miss a substantial number of AMI cases, and the APACE criteria triage only a quarter of the patients. Second, the ESC 0/3-h algorithm has been the standard of care protocol in many institutions since the development of hs-cTn assays and may be more easily implemented in real-world clinical settings than novel thresholds.2,3 The main limitation of this study is the small sample size and different patient characteristics and AMI prevalence from other studies, which limits the generalizability of our findings. We were unable to validate our findings in another cohort, which may have different diagnostic properties from this study. Nevertheless, our study is hypothesis-generating and paves way for further investigation. Future prospective studies are required to validate if the ESC 0/3-h algorithm can be used in conjunction with the 0/1-h algorithm to improve the triage strategy for patients in the observe-zone. Conflict of interest: none declared. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The data underlying this article will be shared on reasonable request to the corresponding author.