High-sensitivity cardiac troponin (hs-cTn) assays have been used clinically by thousands of physicians in many countries throughout the world since their clinical introduction 7 years ago. In the ...early diagnosis of myocardial infarction (MI), beyond doubt, the most important indication of hs-cTn assays, these simple, inexpensive, and highly reproducible tools complement detailed clinical assessment including chest pain characteristics and the electrocardiogram. Hs-cTn assays for the first time allowed the precise quantification of cardiomyocyte injury around the 99th percentile and thereby substantially increased the accuracy of MI detection from blood obtained at presentation to the emergency department (ED). Higher accuracy at ED presentation enabled the development and extensive validation of early hs-cTn–based diagnostic algorithms, which substantially reduced the time required for the safe rule-out or rule-in of MI. This review summarizes key principles underlying the safe and effective use of hs-cTn in the ED in patients with suspected MI.
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The early triage of patients toward rule-out and rule-in of acute myocardial infarction (AMI) is challenging. Therefore, we aimed to develop a 2-h algorithm that uses high-sensitivity cardiac ...troponin I (hs-cTnI).
We prospectively enrolled 1435 (derivation cohort) and 1194 (external validation cohort) patients presenting with suspected AMI to the emergency department. The final diagnosis was adjudicated by 2 independent cardiologists. hs-cTnI was measured at presentation and after 2 h in a blinded fashion. We derived and validated a diagnostic algorithm incorporating hs-cTnI values at presentation and absolute changes within the first 2 h.
AMI was the final diagnosis in 17% of patients in the derivation and 13% in the validation cohort. The 2-h algorithm developed in the derivation cohort classified 56% of patients as rule-out, 17% as rule-in, and 27% as observation. Resulting diagnostic sensitivity and negative predictive value (NPV) were 99.2% and 99.8% for rule-out; specificity and positive predictive value (PPV) were 95.2% and 75.8% for rule-in. Applying the 2-h algorithm in the external validation cohort, 60% of patients were classified as rule-out, 13% as rule-in, and 27% as observation. Diagnostic sensitivity and NPV were 98.7% and 99.7% for rule-out; specificity and PPV were 97.4% and 82.2% for rule-in. Thirty-day survival was 100% for rule-out patients in both cohorts.
A simple algorithm incorporating hs-cTnI baseline values and absolute 2-h changes allowed a triage toward safe rule-out or accurate rule-in of AMI in the majority of patients.
High-sensitivity cardiac troponin (hs-cTn) assays provide higher diagnostic accuracy for acute myocardial infarction (AMI) when compared with conventional assays, but may result in increased use of ...unnecessary coronary angiographies due to their increased detection of cardiomyocyte injury in conditions other than AMI.
We evaluated the impact of the clinical introduction of high-sensitivity cardiac troponin T (hs-cTnT) on the use of coronary angiography, stress testing, and time to discharge in 2544 patients presenting with symptoms suggestive of AMI to the emergency department (ED) within a multicentre study either before (1455 patients) or after (1089 patients) hs-cTnT introduction. Acute myocardial infarction was more often the clinical discharge diagnosis after hs-cTnT introduction (10 vs. 14%, P < 0.001), while unstable angina less often the clinical discharge diagnosis (14 vs. 9%, P = 0.007). The rate of coronary angiography was similar before and after the introduction of hs-cTnT (23 vs. 23%, P = 0.092), as was the percentage of coronary angiographies showing no stenosis (11 vs. 7%, P = 0.361). In contrast, the use of stress testing was substantially reduced from 29 to 19% (P < 0.001). In outpatients, median time to discharge from the ED decreased by 79 min (P < 0.001). Mean total costs decreased by 20% in outpatients after the introduction of hs-cTnT (P = 0.002).
The clinical introduction of hs-cTn does not lead to an increased or inappropriate use of coronary angiography. Introduction of hs-cTn is associated with an improved rule-out process and thereby reduces the need for stress testing and time to discharge.
www.clinicaltrials.gov. Identifier, NCT00470587.
Abstract Objective We aimed to prospectively derive and validate a novel 1h-algorithm using high-sensitivity cardiac troponin I (hs-cTnI) for early rule-out and rule-in of acute myocardial ...infarction. Methods We performed a prospective multicenter diagnostic study enrolling 1811 patients with suspected acute myocardial infarction. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including coronary angiography, echocardiography, follow-up data, and serial measurements of hs-cTnT (but not hs-cTnI). The hs-cTnI 1h-algorithm, incorporating measurements performed at baseline and absolute changes within 1 hour, was derived in a randomly selected sample of 906 patients (derivation cohort), and then validated in the remaining 905 patients (validation cohort). Results Acute myocardial infarction was the final diagnosis in 18% of patients. After applying the hs-cTnI 1h-algorithm developed in the derivation cohort to the validation cohort, 50.5% of patients could be classified as “rule-out,” 19% as “rule-in,” 30.5% as “observe.” In the validation cohort, the negative predictive value for acute myocardial infarction in the “rule-out” zone was 99.6% (95% confidence interval, 98.4%-100%), and the positive predictive value for acute myocardial infarction in the “rule-in” zone was 73.9% (95% confidence interval, 66.7%-80.2%). Negative predictive value of the 1h-algorithm was higher compared with the classical dichotomous interpretation of hs-cTnI and to the standard of care combining hs-cTnI with the electrocardiogram (both P < .001). Positive predictive value also was higher compared with the standard of care ( P < .001). Conclusion Using a simple algorithm incorporating baseline hs-cTnI values and the absolute change within the first hour allows safe rule-out as well as accurate rule-in of acute myocardial infarction in 70% of patients presenting with suspected acute myocardial infarction.
Objectives The study objective was to validate a new high-sensitivity troponin I (hs-TnI) assay in a clinical protocol for assessing patients who present to the emergency department with chest pain. ...Background Protocols using sensitive troponin assays can accelerate the rule out of acute myocardial infarction in patients with low-risk (suspected) acute coronary syndrome (ACS). Methods This study evaluated 2 prospective cohorts of patients in the emergency department with ACS in an accelerated diagnostic pathway integrating 0- and 2-h hs-TnI results, Thrombolysis In Myocardial Infarction (TIMI) risk scores, and electrocardiography. Strategies to identify low-risk patients incorporated TIMI risk scores = 0 or ≤1. The primary endpoint was a major adverse cardiac event (MACE) within 30 days. Results In the primary cohort, 1,635 patients were recruited and had 30-day follow-up. A total of 247 patients (15.1%) had a MACE. The finding of no ischemic electrocardiogram and hs-TnI ≤26.2 ng/l with the TIMI = 0 and TIMI ≤1 pathways, respectively, classified 19.6% (n = 320) and 41.5% (n = 678) of these patients as low risk; 0% (n = 0) and 0.8% (n = 2) had a MACE, respectively. In the secondary cohort, 909 patients were recruited. A total of 156 patients (17.2%) had a MACE. The TIMI = 0 and TIMI ≤1 pathways classified 25.3% (n = 230) and 38.6% (n = 351), respectively, of these patients as low risk; 0% (n = 0) and 0.8% (n = 1) had a MACE, respectively. Sensitivity, specificity, and negative predictive value for TIMI = 0 in the primary cohort were 100% (95% confidence interval CI: 98.5% to 100%), 23.1% (95% CI: 20.9% to 25.3%), and 100% (95% CI: 98.8% to 100%), respectively. Sensitivity, specificity, and negative predictive value for TIMI ≤1 in the primary cohort were 99.2 (95% CI: 97.1 to 99.8), 48.7 (95% CI: 46.1 to 51.3), and 99.7 (95% CI: 98.9 to 99.9), respectively. Sensitivity, specificity, and negative value for TIMI ≤1 in the secondary cohort were 99.4% (95% CI: 96.5 to 100), 46.5% (95% CI: 42.9 to 50.1), and 99.7% (95% CI: 98.4 to 100), respectively. Conclusions An early-discharge strategy using an hs-TnI assay and TIMI score ≤1 had similar safety as previously reported, with the potential to decrease the observation periods and admissions for approximately 40% of patients with suspected ACS. (Advantageous Predictors of Acute Coronary Syndromes Evaluation APACE Study, NCT00470587 ; A 2hr Accelerated Diagnostic Protocol to Assess patients with chest Pain symptoms using contemporary Troponins as the only biomarker ADAPT: a prospective observational validation study, ACTRN12611001069943 )
Abstract Background High-sensitivity cardiac troponin (hs-cTn) may allow an earlier diagnosis of acute myocardial infarction (AMI). Methods We prospectively enrolled 1148 (derivation cohort) and 517 ...(external validation cohort) unselected patients presenting with suspected AMI to the emergency department. Final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnT was measured at presentation and after 2 hours. A diagnostic algorithm incorporating hs-cTnT values at presentation and absolute changes within the first 2 hours was derived. Results AMI was the final diagnosis in 16% of patients in the derivation and 9.1% in the validation cohort. The 2-hour algorithm developed in the derivation cohort classified 60% of patients as “rule-out,” 16% as “rule-in,” and 24% in the “observational-zone.” Resulting sensitivity and negative predictive value (NPV) were 99.5% and 99.9%, respectively, for rule-out, and specificity and positive predictive value (PPV) were 96% and 78%, respectively, for rule-in. Applying the 2-hour triage algorithm in the external validation cohort, 78% of patients could be classified as “rule-out,” 8% as “rule-in,” and 14% in the “observational-zone.” Resulting sensitivity and NPV were 96% and 99.5%, respectively, for rule-out, and specificity and PPV were 99% and 85%, respectively, for rule-in. Cumulative 30-day survival rates were 100%, 98.9%, and 95.2% ( P < .001), and 100%, 100%, and 95% ( P < .001) in patients classified as “rule-out,” “observational-zone,” and “rule-in” in the 2 cohorts, respectively. Conclusions A simple algorithm incorporating hs-cTnT baseline values and absolute changes over 2 hours allowed a triage toward safe rule-out, or accurate rule-in, of AMI in the vast majority of patients, with only 20% requiring more prolonged monitoring and serial blood sampling.
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.
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.
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