Rapid rule out of acute myocardial infarction using undetectable levels of high-sensitivity cardiac troponin☆
Introduction
Acute myocardial infarction (AMI) is a major cause of death and disability worldwide. Patients with symptoms suggestive of AMI account for about 10% of all emergency department (ED) consultations, even so only 10–20% of them eventually suffer from AMI. Rapid identification of this diagnosis is critical for early treatment and management of these patients [1].
In the early 90s several studies showed that cardiac troponins (cTn) were proteins unique to heart and specific and sensitive biomarkers of myocardial damage [2], [3], [4]. Currently cTn and 12-lead electrocardiogram (ECG) form the diagnostic cornerstones of clinical assessment in the evaluation of chest pain patients [5], [6]. A limitation of conventional cTn assays is their low sensitivity at the time of a patient's presentation, owing to a delayed increase of circulating levels for 3 to 4 h and requiring serial sampling for 6 to 9 h in a significant number of patients [2].
Delays in confirming the diagnosis of AMI (rule in) may increase the risk of complications [7] but also delays in excluding the diagnosis (rule out) interfere with the evaluation of alternative diagnoses and contribute to overcrowding in the ED and increasing the cost to the health care system.
Recent studies reported that using more sensitive cTn assays can improve the accuracy of the diagnosis of AMI at the time of presentation to the ED. However using the conventional cut-off (99th percentile) the sensitivities (often < 90%) are not high enough to allow immediately clinical decision making [8], [9], [10], [11], [12], [13]. In contrast, using undetectable levels of hs-cTnT as the criteria for rule out of AMI at presentation seemed to provide very high sensitivity and NPV in initial pilot studies [8], [10]. Our aim was to evaluate undetectable levels of four hs-cTn assays (hs-cTnT Roche, hs-cTnI Siemens, hs-cTnI Beckman Coulter & hs-cTnI Abbott) for the rapid rule out of AMI.
Section snippets
Study design and population
Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) is an ongoing prospective international multicenter study designed and coordinated by the University Hospital Basel Switzerland [10], [14], [15]. From April 2006 to November 2011, consecutive patients older than 18 years presenting to the ED with symptoms suggestive of AMI with an onset or peak within the last 12 h were recruited, after informed consent was obtained.
Patients with terminal kidney failure requiring regular
Statistical methods
The data are expressed as medians ± interquartile range (IQR) for continuous variables, and for categorical variables as numbers and percentages. Continuous variables were compared with the Mann-Whitney–U test, and categorical variables using the Pearson chi-square test. Kaplan–Meier analysis was performed for the endpoint of death and AMI, and log-rank testing was used to assess statistical significance.
All hypothesis testing was two-tailed and p-value of less than 0.05 was considered
Characteristics of patients
The detailed flow of patients in this observational study is shown in Fig. 1. A total of 2072 consecutive patients had levels of hs-cTnT available, the first 1180 consecutive patients had levels of hs-cTnI (Siemens) available, the first 1151 consecutive patients had levels of hs-cTnI (Beckman Coulter) available and the first 1567 consecutive patients had levels of hs-cTnI (Abbott) available.
Table 1 shows baseline characteristics of all patients in the analysis of hs-cTnT. Baseline
Discussion
This analysis derived from a prospective multicenter study evaluated the criteria of undetectable levels using four different hs-cTn assays as a single variable to rule out the diagnosis of AMI in patients with acute chest pain at the time of presentation to the ED.
We report three major findings that extend and corroborate previous experience with hs-cTn assays [8], [9], [10], [11], [12], [13]. First, the percentage of patients having undetectable levels of hs-cTn at presentation varied
Study limitations
Several limitations of our study merit consideration. First, we analysed the performance of undetectable levels using four different novel hs-cTn assays (hs-cTnT Roche; hs-cTnI Siemens; hs-cTnI Beckman Coulter; hs-cTnI Abbott). As our findings regarding NPV were consistent among the four different assays, we assume that it can be generalized to all hs-cTn assays. Of course, this assumption needs to be confirmed in additional studies. Second, the analysis of the three hs-cTnI assays was based on
Conclusions
In conclusion, undetectable levels of hs-cTnT and hs-cTnI at presentation to the ED of patients with acute chest pain have a very high NPV for AMI, particularly in patients presenting 3 h or more since chest pain onset. Therefore using them as a suitable variable in conjunction with other clinical information including the 12-lead ECG, undetectable levels seem a very safe and effective tool to rule out AMI. This criteria applies to much more patients with hs-cTnT as compared to the investigated
Funding
This study was supported by research grants from the Swiss National Science Foundation (PP00B-102853), the Swiss Heart Foundation, Abbott, Roche, Siemens, and the Department of Internal Medicine, University Hospital Basel.
Conflict of interest
Prof. Mueller has received research grants from the Swiss National Science Foundation (PP00B-102853) and the Swiss Heart Foundation, the StiftungfürkardiovaskuläreForschung Basel, 8sense, Abbott, ALERE, Brahms, Critical Diagnostics, Nanosphere, Roche, Siemens, and the Department of Internal Medicine, of the University Hospital Basel, as well as speaker honoraria from Abbott, ALERE, Brahms, Novartis, Roche, and Siemens. We disclose that Dr. Reichlin has received research grants from the Swiss
Acknowledgements
We thank the patients who participated in the study, the staff of the emergency department, the laboratory technicians (particularly Michael Freese, Claudia Stelzig, Esther Garrido, Irina Klimmeck, Melanie Wieland, Beate Hartmann, Janine Voegele, Ina Ferel, Kirsten Hochholzer, and Fausta Chiaverio) for their most valuable efforts and Pascal Benkert for expert statistical advice.
References (27)
- et al.
Joint ESCAAHAWHFTFftRoMI. Universal definition of myocardial infarction
J Am Coll Cardiol
(2007) - et al.
Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a high-sensitivity assay
J Am Coll Cardiol
(2011) - et al.
Normal plasma levels of cardiac troponin I measured by the high-sensitivity cardiac troponin I access prototype assay and the impact on the diagnosis of myocardial ischemia
J Am Coll Cardiol
(2009) - et al.
Incremental value of copeptin for rapid rule out of acute myocardial infarction
J Am Coll Cardiol
(2009) - et al.
European Society of Cardiology and American College of Cardiology guidelines for redefinition of myocardial infarction: how to use existing assays clinically and for clinical trials
Am Heart J
(2002) - et al.
National Hospital Ambulatory Medical Care Survey: 2005 emergency department summary
Adv Data
(2005) - et al.
Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I
N Engl J Med
(1997) - et al.
Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes
N Engl J Med
(1996) - et al.
Cardiac troponin T levels for risk stratification in acute myocardial ischemia. GUSTO IIA Investigators
N Engl J Med
(1996) - et al.
Recommendations for the use of cardiac troponin measurement in acute cardiac care
Eur Heart J
(2010)
Missed diagnoses of acute cardiac ischemia in the emergency department
N Engl J Med
Analytical validation of a high-sensitivity cardiac troponin T assay
Clin Chem
Early diagnosis of myocardial infarction with sensitive cardiac troponin assays
N Engl J Med
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Additive value of bioclinical risk scores to high sensitivity troponins-only strategy in acute coronary syndrome
2021, Clinica Chimica ActaCitation Excerpt :Diagnostic accuracy of hs-cTnT for single measurement was comparable with that provided by hs-cTnI (0.76 vs 0.77, respectively). These AUC values were lower than AUC obtained with HEART score in our study, as well as with those reported in the literature [8,25–26]. The hs-cTn-only strategy would have “ruled out” fewer patients than HEART score, but offered a better risk stratification to GRACE, TIMI and CCS scores with a miss rate of AMI of 0%.
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Clinical Trial Registration-URL:htpp://www.clinicaltrials.gov.
Unique identifier: NCT00470587.
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Both authors have contributed equally and should be considered first author.