Two-hour algorithm for triage toward rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T

BACKGROUND: The early triage of patients toward ruleout 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). METHODS: 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 hscTnI values at presentation and absolute changes within the first 2 h. RESULTS: 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. CONCLUSIONS: A simple algorithm incorporating hscTnI 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

Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays

Aims Several high-sensitivity cardiac troponin (hs-cTn) assays have recently been developed. It is unknown which hs-cTn provides the most accurate prognostic information and to what extent early changes in hs-cTn predict mortality. Methods and results In a prospective, international multicentre study, cTn was simultaneously measured with three novel [high-sensitivity cardiac Troponin T (hs-cTnT), Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI, Siemens] and a conventional assay (cTnT, Roche Diagnostics) in a blinded fashion in 1117 unselected patients with acute chest pain. Patients were followed up 2 years regarding mortality. Eighty-two (7.3%) patients died during the follow-up. The 2-year prognostic accuracy of hs-cTn was most accurate for hs-cTnT [area under the receivers operating characteristic curve (AUC) 0.78 (95% CI: 0.73-0.83) and outperformed both hs-cTnI (Beckman-Coulter, 0.71 (95% CI: 0.65-0.77; P = 0.001 for comparison), hs-cTnI (Siemens) 0.70 (95% CI: 0.64-0.76; P < 0.001 for comparison)] and cTnT 0.67 (95% CI: 0.61-0.74; P < 0.001 for comparison). Absolute changes of hs-cTnT were more accurate than relative changes in predicting mortality, but inferior to presentation values of hs-cTnT. Combining changes of hs-cTnT within the first 6 h with their presentation values did not further improve prognostic accuracy. Similar results were obtained for both hs-cTnI assays regarding the incremental value of changes. Hs-cTn concentrations remained predictors of death in clinically challenging subgroups such as patients with pre-existing coronary artery disease, impaired renal function, and patients older than 75 years. Conclusion High-sensitivity cardiac Troponin T is more accurate than hs-cTnI in the prediction of long-term mortality. Changes of hs-cTn do not seem to further improve risk stratification beyond initial presentation value

Consideration of high-sensitivity troponin values below the 99th percentile at presentation: does it improve diagnostic accuracy?

The introduction of high-sensitivity cardiac troponin (hs-cTn) assays allows the assessment of clinical decision values below the 99th percentile.Final diagnosis and one-year mortality were adjudicated in a multicenter, prospective cohort of 1181 patients presenting with acute chest pain to the emergency department. Hs-cTnT (Roche) and cTnI-ultra (Siemens) were measured in a blinded fashion.At presentation hs-cTnT and cTnI-ultra were below the limit of blank (LOB) in 201 (17%) and 549 (47%) patients, below the 75th percentile in 379 (32%) and 623 (53%) patients, below the 95th percentile in 603 (51%) and 808 (68%), and below the 99th percentile in 748 (63%) and 913 (77%), respectively. Sensitivities for the diagnosis of AMI were 100.0% and 96.8% respectively for hs-cTnT and cTnI-ultra (LOB as cut-off value), 99.5% and 96.2% (75th percentile), 96.8% and 93.0% (95th percentile), and 94.1% and 88.1% (99th percentile). The proportion of patients correctly classified as having or not AMI increased from 32.9% (LOB as cut-off value) to 47.8% (75th percentile), 65.9% (95th percentile) and 77.3% (99th percentile) for hs-cTnT and from 61.2% to 67.3%, 81.9% and 89.3% respectively for cTnI-ultra. At 1 year, all-cause mortality was very low and similar for patients below all of these cut-off levels (between 0.7% and 1.5%, p=0.748 for all-groups comparison).cTn should be considered as a continuous variable. Decision values below the 99th percentile (e.g. the 75th percentile) are associated with a very high NPV for the diagnosis of AMI, but have a lower accuracy than the 99th percentile

Heart-type fatty acid-binding protein in the early diagnosis of acute myocardial infarction

To investigate the diagnostic and prognostic role of heart-type fatty acid-binding protein (hFABP) compared with copeptin and in addition to high-sensitivity cardiac troponin T (hs-cTnT) in patients with chest pain suspected of acute myocardial infarction (AMI).Diagnostic and prognostic performances of hFABP, copeptin and hs-cTnT were evaluated and compared. The final diagnosis was adjudicated by two independent cardiologists.This prospective observational multicentre study took place in four primary and one secondary hospital from April 2006 to September 2009.We enrolled 1247 consecutive patients with suspected AMI to the emergency department. For analysis, patients were included, if baseline levels for hs-cTnT and hFABP were available (n=1074), patients with ST-segment elevation myocardial infarction (STEMI) were excluded for the diagnostic analysis (n=43).Treatment was left to the discretion of the emergency physician.AMI and mortality.4% of the patients had STEMI and 16% of the patients had non-STEMI. Patients with AMI had significantly higher levels of hFABP at presentation (p0.05). The negative predictive value regarding 90-day, 1-year and 2-year mortality was 100% (99-100), 99% (98-100) and 98% (96-99), respectively, for hFABP levels below the median (

Uric acid for diagnosis and risk stratification in suspected myocardial infarction

Hypoxia precedes cardiomyocyte necrosis in acute myocardial infarction (AMI). We therefore hypothesized that uric acid - as a marker of oxidative stress and hypoxia - might be useful in the early diagnosis and risk stratification of patients with suspected AMI.In this prospective observational study, uric acid was measured at presentation in 892 consecutive patients presenting to the emergency department with suspected AMI. The final diagnosis was adjudicated by two independent cardiologists. Patients were followed 24\ua0months regarding mortality. Primary outcome was the diagnosis of AMI, secondary outcome was short- and long-term mortality.Uric acid at presentation was higher in patients with AMI than in patients without (372\ua0μM vs. 336\ua0μM; P\ua

Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction.

AIMS: 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. METHODS AND RESULTS: 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). CONCLUSION: 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.R.T. reports speaker honoraria from B.R.A.H.M.S. and Roche. T.R. reports grants from Swiss National Science Foundation (PASMP3-136995) as well as personal fees from Swiss Heart Foundation and from Goldschmidt-Jacobson Foundation. C.M. reports research grants from the Swiss National Science Foundation, the European Union, the KTI, and the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, 8sense, Abbott, ALERE, Astra Zeneca, Beckman Coulter, Biomerieux, Brahms, Critical Diagnostics,Nanosphere, Roche, Siemens, Singulex, and the University Hospital Basel, as well as speaker honoraria from Abbott, ALERE, Astra Zeneca, BG medicine, Biomerieux, BMS, Brahms, Cardiorentis, Daiichi Sankyo, Novartis, Radiometer, Roche, Sanofi, Siemens, and Singulex

Early diagnosis of myocardial infarction using absolute and relative changes in cardiac troponin concentrations

Absolute changes in high-sensitivity cardiac troponin T (hs-cTnT) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infarction compared with relative changes. It is unknown whether the same applies to high-sensitivity cardiac troponin I (hs-cTnI) assays and whether the combination of absolute and relative change might further increase accuracy.In a prospective, international multicenter study, high-sensitivity cardiac troponin (hs-cTn) was measured with 3 novel assays (hs-cTnT, Roche Diagnostics Corp, Indianapolis, Ind; hs-cTnI, Beckman Coulter Inc, Brea, Calif; hs-cTnI, Siemens, Munich, Germany) in a blinded fashion at presentation and after 1 and 2 hours in a blinded fashion in 830 unselected patients with suspected acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists.The area under the receiver operating characteristic curve for diagnosing acute myocardial infarction was significantly higher for 1- and 2-hour absolute versus relative hs-cTn changes for all 3 assays (P < .001). The area under the receiver operating characteristic curve of the combination of 2-hour absolute and relative change (hs-cTnT 0.98 [95% confidence interval {CI}, 0.97-0.99]; hs-cTnI, Beckman Coulter Inc, 0.97 [95% CI, 0.96-0.99]; hs-cTnI, Siemens, 0.96 [95% CI, 0.93-0.99]) were high and provided some benefit compared with the use of absolute change alone for hs-cTnT, but not for the hs-cTnI assays. Reclassification analysis confirmed the superiority of absolute changes versus relative changes.Absolute changes seem to be the preferred metrics for both hs-cTnT and hs-cTnI in the early diagnosis of acute myocardial infarction. The combination of absolute and relative changes provides a small added value for hs-cTnT, but not for hs-cTnI

Sex-specific chest pain characteristics in the early diagnosis of acute myocardial infarction

Whether sex-specific chest pain characteristics (CPCs) would allow physicians in the emergency department to differentiate women with acute myocardial infarction (AMI) from women with other causes of acute chest pain more accurately remains unknown. OBJECTIVE To improve the management of suspected AMI in women by exploring sex-specific CPCs.From April 21, 2006, through August 12, 2012, we enrolled 2475 consecutive patients (796 women and 1679 men) presenting with acute chest pain to 9 emergency departments in a prospective multicenter study. The final diagnosis of AMI was adjudicated by 2 independent cardiologists.Treatment of AMI in the emergency department.Sex-specific diagnostic performance of 34 predefined and uniformly recorded CPCs in the early diagnosis of AMI.Acute myocardial infarction was the adjudicated final diagnosis in 143 women (18.0%) and 369 men (22.0%). Although most CPCs were reported with similar frequency in women and men, several CPCs were reported more frequently in women (

Serial changes in high-sensitivity cardiac troponin I in the early diagnosis of acute myocardial infarction

Current guidelines require a change (rise and/or fall) in levels of cardiac troponin (cTn) for the diagnosis of acute myocardial infarction (AMI). It is unknown whether absolute or relative changes provide higher accuracy when using high-sensitivity cTnI assays.In a prospective international multicentre study, we assessed the diagnostic accuracy of early absolute and relative changes in cTnI measured with two novel pre-commercial high-sensitivity assays (Siemens and Beckman Coulter) in 943 unselected patients presenting to the ED with suspected AMI. The final diagnosis of AMI was adjudicated using all available data including serial hs-cTnT levels by two independent cardiologists.The diagnostic accuracy of absolute changes in the diagnosis of AMI as quantified by the area under the receiver operating characteristics curve (AUC) was very high (e.g. at 2 h, Siemens high-sensitivity cTnI AUC 0.93, 95%Cl 0.90-0.96; Beckman Coulter high-sensitivity cTnI AUC 0.93, 95%Cl 0.90-0.96) and superior to relative changes at all time points (p < 0.001). The results were consistent in clinically important subgroups. Direct comparison of the absolute changes in the two high-sensitivity cTnI assays showed similar accuracy. When combined with the baseline cTnI levels, the difference between absolute and relative changes became much smaller and remained statistically significant only for the Siemens assay.As single variables early absolute changes in high-sensitivity cTnI levels have significantly higher diagnostic accuracy than relative changes. When combined with the baseline cTn level, reflecting clinical practice, both absolute and relative changes provided very high accuracy with much smaller differences between both approaches