Abstract and Introduction
Abstract
Aims We sought to examine the diagnostic and prognostic utility of sensitive cardiac troponin (cTn) assays in patients with pre-existing coronary artery disease (CAD).
Methods and results We conducted a multicentre study to examine the diagnostic accuracy of one high-sensitive and two sensitive cTn assays in 1098 consecutive patients presenting with symptoms suggestive of acute myocardial infarction (AMI), of whom 401 (37%) had pre-existing CAD. Measurements of Roche high-sensitive cTnT (hs-cTnT), Siemens cTnI-Ultra, Abbott-Architect cTnI and the standard assay (Roche cTnT) were performed in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. Acute myocardial infarction was the final diagnosis in 19% of CAD patients. Among patients with diagnoses other than AMI, baseline cTn levels were elevated above the 99th percentile with Roche hs-cTnT in 40%, with Siemens TnI-Ultra in 15%, and Abbott-Architect cTnI in 13% of them. In patients with pre-existing CAD, the diagnostic accuracy at presentation, quantified by the area under the receiver operator characteristic curve (AUC), was significantly greater for the sensitive cTn assays compared with the standard assay (AUC for Roche hs-cTnT, 0.92; Siemens cTnI-Ultra, 0.94; and Abbott-Architect cTnI, 0.93 vs. AUC for the standard assay, 0.87; P < 0.01 for all comparisons). Elevated levels of cTn measured with the sensitive assays predicted mortality irrespective of pre-existing CAD, age, sex, and cardiovascular risk factors.
Conclusion Sensitive cTn assays have high-diagnostic accuracy also in CAD patients. Mild elevations are common in non-AMI patients and test-specific optimal cut-off levels tend to be higher in CAD patients than in patients without history of CAD. Sensitive cTn assays also retain prognostic value. (ClinicalTrials.gov number, NCT00470587).
Introduction
Acute myocardial infarction (AMI) is a major cause of death and disability. Its rapid and accurate diagnosis is critical for effective evidence-based medical management and treatment, but still an unmet clinical need. Delayed 'rule-in' increases morbidity and mortality, particularly in patients with pre-existing coronary artery disease (CAD). Delayed 'rule-out' prolongs the time spent in the emergency department (ED), increasing patients' anxiety, and causes enormous costs for the health-care system.
More sensitive cardiac troponin (cTn) assays with a limit of detection (LoD) below the 99th percentile of a reference population and improved precision have recently become available in clinical practice. These assays improved the early diagnosis of AMI in unselected patients with acute chest pain. However, their diagnostic accuracy in patients with pre-existing CAD is uncertain, as recently elevated cTn levels were found in >10% of patients with stable CAD.
Also for several other reasons, patients with pre-existing CAD merit particular attention. First, they are at increased risk for both AMI as well as anxiety related to non-cardiac causes of chest pain. Secondly, interpretation of a 12-lead electrocardiography (ECG) is challenging in these patients: pre-existing ST-segment and T-wave alterations are frequent, and new ST-segment elevation is less common in patients with pre-existing CAD. Thirdly, the utility of CT angiography is considerably reduced in such patients. Fourthly, the impact of myocardial loss is particularly devastating when the ventricles have already suffered previous assaults, and delayed diagnosis of AMI yields especially severe consequences. We therefore examined the diagnostic performance of more sensitive cTn assays for the early diagnosis of AMI in patients with pre-existing CAD, presenting with acute chest pain to the ED.