URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.

No abstract

Diagnostic accuracy and clinical utility of the novel Siemens-hs-cTnI-Centaur assay are high and comparable with the established hs-cTn assays. ClinicalTrials.gov Identifier: NCT00470587.

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.

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.

No abstract

The uniform 99th percentile should remain the standard of care when using hs-cTnT levels for the diagnosis of AMI.

P atients with symptoms suggestive of acute myocardial infarction (AMI) account for ≈10% of all emergency department (ED) presentations. 1 The majority of patients are finally found to have diagnoses other than AMI. 2 Thus, the expeditious evaluation of such patients is important because delays in ruling out AMI may interfere with the detection of other underlying diseases. The 0/1 hour (0/1h) algorithm and the 0/3 hour (0/3h) algorithm are both recommended by the European Society of Cardiology with a Class I recommendation for the early rule-out of AMI. 1 The 0/1h algorithm and 0/3h algorithm are completely different protocols. Whereas the 0/1h algorithm uses high-sensitivity cardiac troponin (hs-cTn) concentrations at presentation and absolute changes within the first hour and hence takes optimal advantage of the increased diagnostic accuracy and precision of hs-cTn assays, the 0/3h algorithm uses a fixed threshold protocol based on the 99th percentile at presentation and 3 hours in conjunction with clinical criteria (GRACE [Global Registry of Acute Coronary Events] score <140 and the need to be pain free). It is currently unknown whether 1 algorithm is preferable to the other. The aim of this study was to directly compare safety, quantified by the negative predictive value (NPV) and the negative likelihood ratio (LR) for the presence of AMI, and efficacy, quantified by the proportion of patients triaged toward rule-out in a large diagnostic multicenter study enrolling patients presenting with suspected AMI to the ED (URL: https://www.clinicaltrials.gov. Unique identifier: NCT00470587). The study was carried out according to the principles of the Declaration of Helsinki and approved by the local ethics committees. Written informed consent was obtained from all patients. Patients presenting with ST-segment-elevation MI were excluded. Triage toward rule-out by the 0/1h or the 0/3h algorithm was compared against the final adjudication performed by 2 independent cardiologists using all information, including cardiac imaging and serial hs-cTnT measurements. Analyses were performed with hs-cTnT and hs-cTnI. NPV and efficacy were compared by the McNemar test and Pearson χ 2 test, respectively. The 95% confidence intervals (CIs) were calculated with the Wilson score method without continuity correction. Among 2547 patients eligible for analysis with hs-cTnT, AMI was the final adjudicated diagnosis in 387 patients (15%). The 0/1h algorithm provided safety similar to that of the 0/3h algorithm (NPV, 99.8% [95% CI, 99.4-99.9] and negative LR, 0.01 [95% CI, 0.00-0.03] versus NPV, 99.7% [95% CI, 99.2-99.9] and negative LR, 0.02 [95% CI, 0.00-0.05]) but allowed the rule-out of significantly more patients compared with the 0/3h algorithm (60% versus 44%; P<0.001). Among 2197 patients eligible for analysis with hs-cTnI, AMI was the final diagnosis in 327 patients (15%). The 0/1h algorithm provided higher safety compared with the 0/3h algorithm (NPV, 99.6% [95% CI, 99.1-99.9%] and negative LR, 0.02 [95% CI, 0.01-0.05] versus NP...