High-sensitivity assays for cardiac troponin T (hs-cTnT) are sometimes used to rapidly rule out acute myocardial infarction (AMI).
To estimate the ability of a single hs-cTnT concentration below the ...limit of detection (<0.005 µg/L) and a nonischemic electrocardiogram (ECG) to rule out AMI in adults presenting to the emergency department (ED) with chest pain.
EMBASE and MEDLINE without language restrictions (1 January 2008 to 14 December 2016).
Cohort studies involving adults presenting to the ED with possible acute coronary syndrome in whom an ECG and hs-cTnT measurements were obtained and AMI outcomes adjudicated during initial hospitalization.
Investigators of studies provided data on the number of low-risk patients (no new ischemia on ECG and hs-cTnT measurements <0.005 µg/L) and the number who had AMI during hospitalization (primary outcome) or a major adverse cardiac event (MACE) or death within 30 days (secondary outcomes), by risk classification (low or not low risk). Two independent epidemiologists rated risk of bias of studies.
Of 9241 patients in 11 cohort studies, 2825 (30.6%) were classified as low risk. Fourteen (0.5%) low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7% (95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%; pooled sensitivity was 98.0% (CI, 94.7% to 99.3%). No low-risk patients died.
Few studies, variation in timing and methods of reference standard troponin tests, and heterogeneity of risk and prevalence of AMI across studies.
A single hs-cTnT concentration below the limit of detection in combination with a nonischemic ECG may successfully rule out AMI in patients presenting to EDs with possible emergency acute coronary syndrome.
Emergency Care Foundation.
It is unknown whether more sensitive cardiac troponin (cTn) assays maintain their clinical utility in patients with renal dysfunction. Moreover, their optimal cutoff levels in this vulnerable patient ...population have not previously been defined.
In this multicenter study, we examined the clinical utility of 7 more sensitive cTn assays (3 sensitive and 4 high-sensitivity cTn assays) in patients presenting with symptoms suggestive of acute myocardial infarction. Among 2813 unselected patients, 447 (16%) had renal dysfunction (defined as Modification of Diet in Renal Disease-estimated glomerular filtration rate <60 mL·min(-1)·1.73 m(-2)). The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including coronary angiography and serial levels of high-sensitivity cTnT. Acute myocardial infarction was the final diagnosis in 36% of all patients with renal dysfunction. Among patients with renal dysfunction and elevated baseline cTn levels (≥99th percentile), acute myocardial infarction was the most common diagnosis for all assays (range, 45%-80%). In patients with renal dysfunction, diagnostic accuracy at presentation, quantified by the area under the receiver-operator characteristic curve, was 0.87 to 0.89 with no significant differences between the 7 more sensitive cTn assays and further increased to 0.91 to 0.95 at 3 hours. Overall, the area under the receiver-operator characteristic curve in patients with renal dysfunction was only slightly lower than in patients with normal renal function. The optimal receiver-operator characteristic curve-derived cTn cutoff levels in patients with renal dysfunction were significantly higher compared with those in patients with normal renal function (factor, 1.9-3.4).
More sensitive cTn assays maintain high diagnostic accuracy in patients with renal dysfunction. To ensure the best possible clinical use, assay-specific optimal cutoff levels, which are higher in patients with renal dysfunction, should be considered.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.
Cardiac troponins (cTn) I and T are organ-specific, but not disease specific biomarkers. Although acute myocardial infarction (AMI) is the most important cause of cTn elevation, other cardiac ...disorders as well as primarily noncardiac disorders with cardiac involvement often are also associated with cardiomyocyte injury. Levels of cTn should be interpreted as quantitative markers of cardiomyocyte injury with the likelihood of AMI increasing with the level of cTn.
Similar to the level of cTn at presentation, acute changes in cTn help to differentiate chronic disorders, which show no change, from acute conditions, which usually show a rise from presentation to the second measurement at 1–3h in the emergency department. Thereby, changes in cTn help to overcome some of the challenges posed by cTn elevations in non-AMI patients. Absolute changes in cTn provide a higher diagnostic accuracy for AMI as compared to relative changes. Again, the higher the absolute change, the higher the likelihood for AMI. Two caveats apply to the diagnostic use of cTn changes. First, patients with AMI may show no or only a minimal change when assessed around the peak of cTn release. Second, in addition to AMI, several other acute cardiac conditions including tachyarrhythmias, myocarditis, hypertensive crisis, and Takotsubo cardiomyopathy also may present with substantial cTn changes.
•Changes in cardiac troponin provide additional information in diagnosis of AMI.•Changes in troponin levels help to handle the challenges posed by troponin elevations in non-AMI.•Absolute changes provide higher diagnostic accuracy for AMI as compared to relative changes.
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.
This study sought to determine these important real-world outcome data.
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).
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.
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.
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It is unknown whether cardiac troponin (cTn) I or cTnT is the preferred biomarker in the early diagnosis of acute myocardial infarction without ST segment elevation (NSTEMI).
In a prospective ...multicentre study, we measured cTnI and cTnT using clinically available high-sensitivity assays (hs-cTnI Abbott and hs-cTnT Roche) and compared their diagnostic and prognostic accuracies in consecutive patients presenting to the emergency department with acute chest pain. The final diagnosis was adjudicated by two independent cardiologists using all information pertaining to the individual patient. The mean follow-up was 24 months. Among 2226 consecutive patients, 18% had an adjudicated final diagnosis of NSTEMI. Diagnostic accuracy at presentation as quantified by the area under the receiver-operating-characteristics curve (AUC) for NSTEMI was very high and similar for hs-cTnI AUC: 0.93, 95% confidence interval (CI) 0.92-0.94 and hs-cTnT (0.94, 95% CI: 0.92-0.94) P = 0.62. In early presenters (<3 h since chest pain onset) hs-cTnI showed a higher diagnostic accuracy (AUC: 0.92, 95% CI: 0.89-0.94) when compared with hs-cTnT AUC (0.89, 95% CI: 0.86-0.91) (P = 0.019), while hs-cTnT was superior in late presenters AUC hs-cTnT 0.96 (95% CI: 0.94-0.96) vs. hs-cTnI 0.94 (95% CI: 0.93-0.95); P = 0.007. The prognostic accuracy for all-cause mortality, quantified by AUC, was significantly higher for hs-cTnT (AUC: 0.80; 95% CI: 0.78-0.82) when compared with hs-cTnI (AUC: 0.75; 95% CI: 0.73-0.77; P < 0.001).
Both hs-cTnI and hs-cTnT provided high diagnostic and prognostic accuracy. The direct comparison revealed small but potentially important differences that might help to further improve the clinical use of hs-cTn.
The safety of the European Society of Cardiology (ESC) 0/1-h algorithm for rapid rule-out and rule-in of non–ST-segment elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac ...troponin (hs-cTn) has been questioned.
This study aimed to validate the diagnostic performance of the 0/1-h algorithm in a large multicenter study.
The authors prospectively enrolled unselected patients in 6 countries presenting to the emergency department with symptoms suggestive of NSTEMI. Final diagnosis was centrally adjudicated by 2 independent cardiologists. Hs-cTnT and hs-cTnI blood concentrations were measured at presentation and after 1 h. Safety of rule-out was quantified by the negative predictive value (NPV) for NSTEMI, accuracy of rule-in by the positive predictive value (PPV), and overall efficacy by the proportion of patients triaged towards rule-out or rule-in within 1 h.
Prevalence of NSTEMI was 17%. Among 4,368 patients with serial hs-cTnT measurements available, safety of rule-out (NPV 99.8%, 2,488 of 2,493), accuracy of rule-in (PPV 74.5%, 572 of 768), and overall efficacy were high by assigning three-fourths of patients either to rule-out (57%, 2,493 to 4,368) or rule-in (18%, 768 to 4,368). Similarly, among 3,500 patients with serial hs-cTnI measurements, safety of rule-out (NPV 99.7%, 1,528 of 1,533), accuracy of rule-in (PPV 62.3%, 498 of 800), and overall efficacy were high by assigning more than two-thirds of patients either to rule-out (44%, 1,533 of 3,500) or rule-in (23%, 800 of 3,500). Excellent safety was confirmed in multiple subgroup analyses including patients presenting early (≤3 h) after chest pain onset.
The ESC 0/1-h algorithm using hs-cTnT and hs-cTnI is very safe and effective in triaging patients with suspected NSTEMI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation APACE; NCT00470587; and Biomarkers in Acute Cardiac Care BACC; NCT02355457)
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BACKGROUND:The European Society of Cardiology recommends a 0/1-hour algorithm for rapid rule-out and rule-in of non–ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin ...(hs-cTn) concentrations irrespective of renal function. Because patients with renal dysfunction (RD) frequently present with increased hs-cTn concentrations even in the absence of non–ST-segment elevation myocardial infarction, concern has been raised regarding the performance of the 0/1-hour algorithm in RD.
METHODS:In a prospective multicenter diagnostic study enrolling unselected patients presenting with suspected non–ST-segment elevation myocardial infarction to the emergency department, we assessed the diagnostic performance of the European Society of Cardiology 0/1-hour algorithm using hs-cTnT and hs-cTnI in patients with RD, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m, and compared it to patients with normal renal function. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including cardiac imaging. Safety was quantified as sensitivity in the rule-out zone, accuracy as the specificity in the rule-in zone, and efficacy as the proportion of the overall cohort assigned to either rule-out or rule-in based on the 0- and 1-hour sample.
RESULTS:Among 3254 patients, RD was present in 487 patients (15%). The prevalence of non–ST-segment elevation myocardial infarction was substantially higher in patients with RD compared with patients with normal renal function (31% versus 13%, P<0.001). Using hs-cTnT, patients with RD had comparable sensitivity of rule-out (100.0% 95% confidence interval {CI}, 97.6–100.0 versus 99.2% 95% CI, 97.6–99.8; P=0.559), lower specificity of rule-in (88.7% 95% CI, 84.8–91.9 versus 96.5% 95% CI, 95.7–97.2; P<0.001), and lower overall efficacy (51% versus 81%, P<0.001), mainly driven by a much lower percentage of patients eligible for rule-out (18% versus 68%, P<0.001) compared with patients with normal renal function. Using hs-cTnI, patients with RD had comparable sensitivity of rule-out (98.6% 95% CI, 95.0–99.8 versus 98.5% 95% CI, 96.5–99.5; P=1.0), lower specificity of rule-in (84.4% 95% CI, 79.9–88.3 versus 91.7% 95% CI, 90.5–92.9; P<0.001), and lower overall efficacy (54% versus 76%, P<0.001; proportion ruled out, 18% versus 58%, P<0.001) compared with patients with normal renal function.
CONCLUSIONS:In patients with RD, the safety of the European Society of Cardiology 0/1-hour algorithm is high, but specificity of rule-in and overall efficacy are decreased. Modifications of the rule-in and rule-out thresholds did not improve the safety or overall efficacy of the 0/1-hour algorithm.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT00470587.
Until now, high-sensitivity cardiac troponin (hs-cTn) assays were mainly developed for large central laboratory platforms.
This study aimed to assess the clinical performance of a point-of-care ...(POC)-hs-cTnI assay in patients with suspected myocardial infarction (MI).
This study enrolled patients presenting to the emergency department with symptoms suggestive of MI. Two cardiologists centrally adjudicated the final diagnosis using all clinical data including cardiac imaging. The primary objective was to directly compare diagnostic accuracy of POC-hs-cTnI-TriageTrue versus best-validated central laboratory assays. Secondary objectives included the derivation and validation of a POC-hs-cTnI-TriageTrue–specific 0/1-h algorithm.
MI was the adjudicated final diagnosis in 178 of 1,261 patients (14%). The area under the curve (AUC) for POC-hs-cTnI-TriageTrue at presentation was 0.95 (95% confidence interval CI: 0.93 to 0.96) and was at least comparable to hs-cTnT-Elecsys (AUC: 0.94; 95% CI: 0.93 to 0.96; p = 0.213) and hs-cTnI-Architect (AUC: 0.92; 95% CI: 0.90 to 0.93; p < 0.001). A single cutoff concentration <3 ng/l at presentation identified 45% of patients at low risk with a negative predictive value (NPV) of 100% (95% CI: 99.4% to 100%). A single cutoff concentration >60 ng/l identified patients at high risk with a positive predictive value (PPV) of 76.8% (95% CI: 68.9% to 83.6%). The 0/1-h algorithm ruled out 55% of patients (NPV: 100%; 95% CI: 98.8% to 100%), and ruled in 18% of patients (PPV: 76.8%; 95% CI: 67.2% to 84.7%). Ruled-out patients had cumulative event rates of 0% at 30 days and 1.6% at 2 years. This study confirmed these findings in a secondary analysis including hs-cTnI-Architect for central adjudication.
The POC-hs-cTnI-TriageTrue assay provides high diagnostic accuracy in patients with suspected MI with a clinical performance that is at least comparable to that of best-validated central laboratory assays. (Advantageous Predictors of Acute Coronary Syndromes Evaluation Study APACE; NCT00470587)
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We aimed to prospectively validate a novel 1-hour algorithm using high-sensitivity cardiac troponin T measurement for early rule-out and rule-in of acute myocardial infarction (MI).
In a multicentre ...study, we enrolled 1320 patients presenting to the emergency department with suspected acute MI. The high-sensitivity cardiac troponin T 1-hour algorithm, incorporating baseline values as well as absolute changes within the first hour, was validated against the final diagnosis. The final diagnosis was then adjudicated by 2 independent cardiologists using all available information, including coronary angiography, echocardiography, follow-up data and serial measurements of high-sensitivity cardiac troponin T levels.
Acute MI was the final diagnosis in 17.3% of patients. With application of the high-sensitivity cardiac troponin T 1-hour algorithm, 786 (59.5%) patients were classified as "rule-out," 216 (16.4%) were classified as "rule-in" and 318 (24.1%) were classified to the "observational zone." The sensitivity and the negative predictive value for acute MI in the rule-out zone were 99.6% (95% confidence interval CI 97.6%-99.9%) and 99.9% (95% CI 99.3%-100%), respectively. The specificity and the positive predictive value for acute MI in the rule-in zone were 95.7% (95% CI 94.3%-96.8%) and 78.2% (95% CI 72.1%-83.6%), respectively. The 1-hour algorithm provided higher negative and positive predictive values than the standard interpretation of highsensitivity cardiac troponin T using a single cut-off level (both p < 0.05). Cumulative 30-day mortality was 0.0%, 1.6% and 1.9% in patients classified in the rule-out, observational and rule-in groups, respectively (p = 0.001).
This rapid strategy incorporating high-sensitivity cardiac troponin T baseline values and absolute changes within the first hour substantially accelerated the management of suspected acute MI by allowing safe rule-out as well as accurate rule-in of acute MI in 3 out of 4 patients.
ClinicalTrials.gov, NCT00470587.
BACKGROUND:Cardiac myosin-binding protein C (cMyC) is a cardiac-restricted protein that is more abundant than cardiac troponins (cTn) and is released more rapidly after acute myocardial infarction ...(AMI). We evaluated cMyC as an adjunct or alternative to cTn in the early diagnosis of AMI.
METHODS:Unselected patients (N=1954) presenting to the emergency department with symptoms suggestive of AMI, concentrations of cMyC, and high-sensitivity (hs) and standard-sensitivity cTn were measured at presentation. The final diagnosis of AMI was independently adjudicated using all available clinical and biochemical information without knowledge of cMyC. The prognostic end point was long-term mortality.
RESULTS:Final diagnosis was AMI in 340 patients (17%). Concentrations of cMyC at presentation were significantly higher in those with versus without AMI (median, 237 ng/L versus 13 ng/L, P<0.001). Discriminatory power for AMI, as quantified by the area under the receiver-operating characteristic curve (AUC), was comparable for cMyC (AUC, 0.924), hs-cTnT (AUC, 0.927), and hs-cTnI (AUC, 0.922) and superior to cTnI measured by a contemporary sensitivity assay (AUC, 0.909). The combination of cMyC with hs-cTnT or standard-sensitivity cTnI (but not hs-cTnI) led to an increase in AUC to 0.931 (P<0.0001) and 0.926 (P=0.003), respectively. Use of cMyC more accurately classified patients with a single blood test into rule-out or rule-in categoriesNet Reclassification Improvement +0.149 versus hs-cTnT, +0.235 versus hs-cTnI (P<0.001). In early presenters (chest pain <3 h), the improvement in rule-in/rule-out classification with cMyC was larger compared with hs-cTnT (Net Reclassification Improvement +0.256) and hs-cTnI (Net Reclassification Improvement +0.308; both P<0.001). Comparing the C statistics, cMyC was superior to hs-cTnI and standard sensitivity cTnI (P<0.05 for both) and similar to hs-cTnT at predicting death at 3 years.
CONCLUSIONS:cMyC at presentation provides discriminatory power comparable to hs-cTnT and hs-cTnI in the diagnosis of AMI and may perform favorably in patients presenting early after symptom onset.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT00470587.
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