Clinical Use of a New High-Sensitivity Cardiac Troponin I Assay in Patients with Suspected Myocardial Infarction.

BACKGROUND: We aimed to validate the clinical performance of the high-sensitivity cardiac troponin I [VITROS® Immunodiagnostic Products hs Troponin I (hs-cTnI-VITROS)] assay. METHODS: We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists considering all clinical information, including cardiac imaging: first, using serial hs-cTnT-Elecsys (primary analysis) and, second, using hs-cTnI-Architect (secondary analysis) measurements in addition to the clinically used (hs)-cTn. hs-cTnI-VITROS was measured at presentation and at 1 h in a blinded fashion. The primary objective was direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI-VITROS vs hs-cTnT-Elecsys and hs-cTnI-Architect, and in a subgroup also hs-cTnI-Centaur and hs-cTnI-Access. Secondary objectives included the derivation and validation of an hs-cTnI-VITROS-0/1-h algorithm. RESULTS: AMI was the adjudicated final diagnosis in 158 of 1231 (13%) patients. At presentation, the AUC for hs-cTnI-VITROS was 0.95 (95% CI, 0.93-0.96); for hs-cTnT-Elecsys, 0.94 (95% CI, 0.92-0.95); and for hs-cTnI-Architect, 0.92 (95% CI, 0.90-0.94). AUCs for hs-cTnI-Centaur and hs-cTnI-Access were 0.95 (95% CI, 0.94-0.97). Applying the derived hs-cTnI-VITROS-0/1-h algorithm (derivation cohort n = 519) to the validation cohort (n = 520), 53% of patients were ruled out [sensitivity, 100% (95% CI, 94.1-100)] and 14% of patients were ruled in [specificity, 95.6% (95% CI, 93.4-97.2)]. Patients ruled out by the 0/1-h algorithm had a survival rate of 99.8% at 30 days. Findings were confirmed in the secondary analyses using the adjudication including serial measurements of hs-cTnI-Architect. CONCLUSIONS: The hs-cTnI-VITROS assay has at least comparable diagnostic accuracy with the currently best validated hs-cTnT and hs-cTnI assays. CLINICALTRIALSGOV IDENTIFIER: NCT00470587.

Two-Hour Algorithm for Rapid Triage of Suspected Acute Myocardial Infarction Using a High-Sensitivity Cardiac Troponin I Assay.

BACKGROUND: We aimed to derive and externally validate a 0/2-h algorithm using the high-sensitivity cardiac troponin I (hs-cTnI)-Access assay. METHODS: We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI) in 2 prospective diagnostic studies using central adjudication. Two independent cardiologists adjudicated the final diagnosis, including all available medical information including cardiac imaging. hs-cTnI-Access concentrations were measured at presentation and after 2 h in a blinded fashion. RESULTS: AMI was the adjudicated final diagnosis in 164 of 1131 (14.5%) patients in the derivation cohort. Rule-out by the hs-cTnI-Access 0/2-h algorithm was defined as 0-h hs-cTnI-Access concentration <4 ng/L in patients with an onset of chest pain >3 h (direct rule-out) or a 0-h hs-cTnI-Access concentration <5 ng/L and an absolute change within 2 h <5 ng/L in all other patients. Derived thresholds for rule-in were a 0-h hs-cTnI-Access concentration ≥50 ng/L (direct rule-in) or an absolute change within 2 h ≥20 ng/L. In the derivation cohort, these cutoffs ruled out 55% of patients with a negative predictive value (NPV) of 99.8% (95% CI, 99.3-100) and sensitivity of 99.4% (95% CI, 96.5-99.9), and ruled in 30% of patients with a positive predictive value (PPV) of 73% (95% CI, 66.1-79). In the validation cohort, AMI was the adjudicated final diagnosis in 88 of 1280 (6.9%) patients. These cutoffs ruled out 77.9% of patients with an NPV of 99.8% (95% CI, 99.3-100) and sensitivity of 97.7% (95% CI, 92.0-99.7), and ruled in 5.8% of patients with a PPV of 77% (95% CI, 65.8-86) in the validation cohort. CONCLUSIONS: Safety and efficacy of the l hs-cTnI-Access 0/2-h algorithm for triage toward rule-out or rule-in of AMI are very high. TRIAL REGISTRATION: APACE, NCT00470587; ADAPT, ACTRN1261100106994; IMPACT, ACTRN12611000206921.

High-Sensitivity Cardiac Troponin I Assay for Early Diagnosis of Acute Myocardial Infarction.

BACKGROUND: The aim of this study was to validate the clinical performance of the Beckman Access high-sensitivity cardiac troponin I (hs-cTnI) assay. METHODS: We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists with all clinical information including cardiac imaging twice: first, using serial hs-cTnT (Elecsys, primary analysis), and second, using hs-cTnI (Architect, secondary analysis) measurements in addition to the clinically used hs-cTn. hs-cTnI Access was measured at presentation and at 1 h. The primary objective was a direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI Access vs the hs-cTnT Elecsys and hs-cTnI Architect assays. Secondary objectives included the derivation and validation of an hs-cTnI Access-specific 0/1-h algorithm. RESULTS: AMI was the adjudicated final diagnosis in 243 of 1579 (15.4%) patients. The AUC at presentation for hs-cTnI Access was 0.95 (95% CI, 0.94-0.96), higher than hs-cTnI Architect [0.92 (95% CI, 0.91-0.94; P < 0.001)] and comparable to hs-cTnT Elecsys [0.94 (95% CI, 0.93-0.95; P = 0.12)]. Applying the derived hs-cTnI Access 0/1-h algorithm (derivation cohort n = 686) to the validation cohort (n = 680), 60% of patients were ruled out [sensitivity, 98.9% (95% CI, 94.3-99.8)], and 15% of patients were ruled in [specificity, 95.9% (95% CI, 94.0-97.2)]. Patients ruled out by the 0/1-h algorithm had a survival rate of 100% at 30 days. Findings were confirmed in the secondary analyses by the adjudication including serial measurements of Architect hs-cTnI. CONCLUSIONS: Diagnostic accuracy and clinical utility of the Beckman hs-cTnI Access assay are very high and at least comparable to Roche hs-cTnT and Abbott hs-cTnI assays. ClinicalTrials.gov Identifier: NCT00470587.

Comparing the utility of clinical risk scores and integrated clinical judgement in patients with suspected acute coronary syndrome.

AIMS: The utility of clinical risk scores regarding the prediction of major adverse cardiac events (MACE) is uncertain. We aimed to directly compare the prognostic performance of five established clinical risk scores as well as an unstructured integrated clinical judgement (ICJ) of the treating emergency department (ED) physician. METHODS AND RESULTS: Thirty-day MACE including all-cause death, life-threatening arrhythmia, cardiogenic shock, acute myocardial infarction (including the index event), and unstable angina requiring urgent coronary revascularization were centrally adjudicated by two independent cardiologists in patients presenting to the ED with acute chest discomfort in an international multicentre study. We compared the prognostic performance of the HEART score, GRACE score, T-MACS, TIMI score, and EDACS, as well as the unstructured ICJ of the treating ED physician (visual analogue scale to estimate the probability of acute coronary syndrome, ranging from 0 to 100). Among 4551 eligible patients, 1110/4551 patients (24.4%) had at least one MACE within 30 days. Prognostic accuracy was high and comparable for the HEART score, GRACE score, T-MACS, and ICJ [area under the receiver operating characteristic curve (AUC) 0.85-0.87] but significantly lower and only moderate for the TIMI score (AUC 0.79, P < 0.001) and EDACS (AUC 0.74, P < 0.001), resulting in sensitivities for the rule-out of 30-day MACE of 93-96, 87 (P < 0.001), and 72% (P < 0.001), respectively. CONCLUSION: The HEART score, GRACE score, T-MACS, and unstructured ICJ of the treating physician, not the TIMI score or EDACS, performed well for the prediction of 30-day MACE and may be considered for routine clinical use. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00470587.

4D-Var Inversion of European NH3 Emissions Using CrIS NH3 Measurements and GEOS-Chem Adjoint With Bi-Directional and Uni-Directional Flux Schemes.

We conduct the first 4D-Var inversion of NH3 accounting for NH3 bi-directional flux, using CrIS satellite NH3 observations over Europe in 2016. We find posterior NH3 emissions peak more in springtime than prior emissions at continental to national scales, and annually they are generally smaller than the prior emissions over central Europe, but larger over most of the rest of Europe. Annual posterior anthropogenic NH3 emissions for 25 European Union members (EU25) are 25% higher than the prior emissions and very close (<2% difference) to other inventories. Our posterior annual anthropogenic emissions for EU25, the UK, the Netherlands, and Switzerland are generally 10%-20% smaller than when treating NH3 fluxes as uni-directional emissions, while the monthly regional difference can be up to 34% (Switzerland in July). Compared to monthly mean in-situ observations, our posterior NH3 emissions from both schemes generally improve the magnitude and seasonality of simulated surface NH3 and bulk NH x wet deposition throughout most of Europe, whereas evaluation against hourly measurements at a background site shows the bi-directional scheme better captures observed diurnal variability of surface NH3. This contrast highlights the need for accurately simulating diurnal variability of NH3 in assimilation of sun-synchronous observations and also the potential value of future geostationary satellite observations. Overall, our top-down ammonia emissions can help to examine the effectiveness of air pollution control policies to facilitate future air pollution management, as well as helping us understand the uncertainty in top-down NH3 emissions estimates associated with treatment of NH3 surface exchange.

Outcome of Applying the ESC 0/1-hour Algorithm in Patients With Suspected Myocardial Infarction.

BACKGROUND: The European Society of Cardiology (ESC) recommends the 0/1-h algorithm for rapid triage of patients with suspected non-ST-segment elevation myocardial infarction (MI). However, its impact on patient management and safety when routinely applied is unknown. OBJECTIVES: This study sought to determine these important real-world outcome data. METHODS: In a prospective international study enrolling patients presenting with acute chest discomfort to the emergency department (ED), the authors assessed the real-world performance of the ESC 0/1-h algorithm using high-sensitivity cardiac troponin T embedded in routine clinical care and its associated 30-day rates of major adverse cardiac events (MACE) (the composite of cardiovascular death and MI). RESULTS: Among 2,296 patients, non-ST-segment elevation MI prevalence was 9.8%. In median, 1-h blood samples were collected 65 min after the 0-h blood draw. Overall, 94% of patients were managed without protocol violations, and 98% of patients triaged toward rule-out did not require additional cardiac investigations including high-sensitivity cardiac troponin T measurements at later time points or coronary computed tomography angiography in the ED. Median ED stay was 2 h and 30 min. The ESC 0/1-h algorithm triaged 62% of patients toward rule-out, and 71% of all patients underwent outpatient management. Proportion of patients with 30-day MACE were 0.2% (95% confidence interval: 03% to 0.5%) in the rule-out group and 0.1% (95% confidence interval: 0% to 0.2%) in outpatients. Very low MACE rates were confirmed in multiple subgroups, including early presenters. CONCLUSIONS: These real-world data document the excellent applicability, short time to ED discharge, and low rate of 30-day MACE associated with the routine clinical use of the ESC 0/1-h algorithm for the management of patients presenting with acute chest discomfort to the ED.

Predicting Major Adverse Events in Patients With Acute Myocardial Infarction.

BACKGROUND: Early and accurate detection of short-term major adverse cardiac events (MACE) in patients with suspected acute myocardial infarction (AMI) is an unmet clinical need. OBJECTIVES: The goal of this study was to test the hypothesis that adding clinical judgment and electrocardiogram findings to the European Society of Cardiology (ESC) high-sensitivity cardiac troponin (hs-cTn) measurement at presentation and after 1 h (ESC hs-cTn 0/1 h algorithm) would further improve its performance to predict MACE. METHODS: Patients presenting to an emergency department with suspected AMI were enrolled in a prospective, multicenter diagnostic study. The primary endpoint was MACE, including all-cause death, cardiac arrest, AMI, cardiogenic shock, sustained ventricular arrhythmia, and high-grade atrioventricular block within 30 days including index events. The secondary endpoint was MACE + unstable angina (UA) receiving early (≤24 h) revascularization. RESULTS: Among 3,123 patients, the ESC hs-cTnT 0/1 h algorithm triaged significantly more patients toward rule-out compared with the extended algorithm (60%; 95% CI: 59% to 62% vs. 45%; 95% CI: 43% to 46%; p < 0.001), while maintaining similar 30-day MACE rates (0.6%; 95% CI: 0.3% to 1.1% vs. 0.4%; 95% CI: 0.1% to 0.9%; p = 0.429), resulting in a similar negative predictive value (99.4%; 95% CI: 98.9% to 99.6% vs. 99.6%; 95% CI: 99.2% to 99.8%; p = 0.097). The ESC hs-cTnT 0/1 h algorithm ruled-in fewer patients (16%; 95% CI: 14.9% to 17.5% vs. 26%; 95% CI: 24.2% to 27.2%; p < 0.001) compared with the extended algorithm, albeit with a higher positive predictive value (76.6%; 95% CI: 72.8% to 80.1% vs. 59%; 95% CI: 55.5% to 62.3%; p < 0.001). For 30-day MACE + UA, the ESC hs-cTnT 0/1 h algorithm had a higher positive predictive value for rule-in, whereas the extended algorithm had a higher negative predictive value for the rule-out. Similar findings emerged when using hs-cTnI. CONCLUSIONS: The ESC hs-cTn 0/1 h algorithm better balanced efficacy and safety in the prediction of MACE, whereas the extended algorithm is the preferred option for the rule-out of 30-day MACE + UA. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587).