Early Rule-Out and Rule-In Strategies for Myocardial Infarction | Clinical Chemistry
Given our understanding of troponin kinetics, a single negative troponin assays The solution is probably a compromise between the two. Cardiac troponin I and T are specific and sensitive biomarkers of cardiac Thygesen K. Myocardial Infarction Type 2 and Myocardial Injury. Of the patients with negative troponin at baseline, 24 (21%) had elevated cTnT levels by in 2 studies to date, which demonstrated that troponin release.
The use of novel biomarkers is also addressed and the combination of biomarkers in accelerated diagnostic strategies discussed. Troponin-Only Strategies for Rapid Rule-In and Rule-Out AMI Contemporary sensitive troponin assays cannot safely rule out AMI at presentation, and therefore international guidelines recommend serial troponin testing, which often requires admission to hospital including placement into observation units High-sensitivity troponin assays have excellent precision at very low concentrations and permit accurate quantification of troponin in the majority of healthy persons 13 These assays have the potential to transform the assessment of patients with chest pain through the development of safe and effective strategies to rule out myocardial infarction MI rapidly in the ED.
Until recently guidelines have recommended measuring troponin on presentation and 6 h later, or 10—12 h after the onset of symptoms, to coincide with the peak in plasma troponin concentrations This minimizes the risk of missing a small myocardial infarct and allows the assessment of infarct size. However, the majority of patients require admission for serial testing, placing pressure on crowded EDs and hospitals.
They concluded that the use of high-sensitivity troponin on presentation and at 3 h was a cost-effective strategy compared to admission of patients for conventional troponin testing at 10—12 h.
The clinical effectiveness and safety of these pathways, as well as the optimal threshold and timing of sampling remain uncertain. There is controversy on how to precisely determine the 99th centile A recent systematic review evaluated the diagnostic accuracy of the high-sensitivity troponin T Roche and high-sensitivity troponin I Abbott using the 99th centile at presentation and at 2—3 h as compared to a contemporary assay at presentation and 10—12 h after symptom onset The majority of published studies are retrospective and observational involving selected patients and prospective clinical trials evaluating the implementation of high-sensitivity troponin assays are awaited.
Some studies recruited low-risk patients and therefore the findings may not be generalizable to all patients presenting with suspected ACS. Most studies did not use the high-sensitivity assay as the reference standard for the primary analysis, and therefore the adjudication of the diagnosis of myocardial infarction was based on peak troponin testing using a conventional assay.
This may lead to overestimation of both the sensitivity and negative predictive value NPV of the high-sensitivity assay. Finally, relatively few studies have addressed important subgroups of patients, such as those who present early and within 3 h of the onset of their symptoms. Interestingly, Pickering et al. Why should we use the same threshold to rule out and diagnose MI when high-sensitivity assays can quantify troponin concentrations well below the 99th centile?
Recent studies have demonstrated that very low troponin concentrations at presentation can be used to risk stratify patients 23 — However, assay imprecision at the limit of blank may result in variation in the performance of this approach in practice, and influence the proportion of patients who could be identified as suitable for discharge.
The only high-sensitivity troponin I assay currently in clinical use manufactured by Abbott Diagnostics has enhanced high-sensitivity troponin I assay precision at very low concentrations, permits quantification of troponin in the majority of persons, and affords the opportunity to define a threshold to rule out MI based on clinical performance rather than analytical imprecision.
Blood test and ECG may safely rule out heart attack
This threshold identified two-thirds of patients with suspected ACS who are low-risk and may be suitable for immediate discharge. The only exception was in the group of patients who present within 2 h of symptom onset where the NPV was lower at A number of pathways have been validated using both high-sensitivity troponin T and troponin I assays with serial testing as early as one hour after presentation. Each of these strategies and pathways show promise, and are likely to improve on the sensitivity and NPV of conventional pathways that rely on the 99th centile to both diagnose and rule out MI.
Implementation of these approaches is likely to reduce healthcare costs by avoiding unnecessary hospitalization.
Prospective studies are now required that evaluate both the clinical and cost effectiveness of implementing these novel pathways in practice.
When clinical reliance rests on the accuracy of reported troponin values, especially at low concentrations, quality assurance measures including accuracy of assay calibration are of the utmost importance 32 Even using a high sensitivity assay, troponin concentrations may take several hours to increase in the circulation following the onset of an AMI.
This creates a period in the first hours after onset where troponin values are below the 99th centile but rising and is the basis of the requirement for serial sampling. Biomarkers that can identify patients with ACS in this early phase could therefore either obviate the need for serial sampling altogether or reduce the time period over which serial sampling takes place. CK-MB and myoglobin are 2 such biomarkers. Unexpectedly positive troponin results occasionally occur in such situations, which may otherwise not be detected.
How do GPs currently request troponin tests? Most requests for troponin testing from general practice are requests for a single test, not serial testing. The suggested time frame varies between publications, but is usually in the order of 6—9 hours 417 with the caveat that the time of symptom onset can be unreliable. Local experts have suggested that a single troponin test 12 hours after resolution of suggestive symptoms with a normal electrocardiogram and no high-risk features is useful for this purpose.
The safest rule of thumb is that a single negative test result for troponin does not exclude AMI in a patient with current or very recent symptoms, nor does it exclude clinically significant coronary artery disease.
Conditions associated with chronic troponin elevation As most GP requests for troponin testing are for a single test, conditions associated with chronic, non-AMI elevation of troponin levels present a problem. Examples include chronic cardiac failure and chronic kidney disease CKD.
A positive result from a single troponin test could be misleading because it might reflect the underlying chronic disease and not AMI.
The prevalence of positive troponin test results defined as above the 99th percentile of the general population in CKD depends on the stage of the CKD positive results are more likely during more advanced stages and on the troponin assay used. This is exemplified by a recent study of asymptomatic patients who had CKD but were not on dialysis.
Early Rule-Out and Rule-In Strategies for Myocardial Infarction
Clinical assessment of the acute event in such patients becomes all the more important if this is to be avoided. Logistics of troponin testing for outpatients Offering troponin testing in the community is logistically complex and there is a lack of formal guidance for laboratories in this area.
Guidelines on management of ACS recommend that a troponin test result should be available within 60 minutes of blood being drawn and, if not, that point-of-care testing should be available.
So what is the solution? Accept the longer turnaround times and promote judicious use of troponin tests by GPs?
Should general practitioners order troponin tests?
Longer turnaround times may be acceptable if testing is largely confined to patients who have a low pretest probability, or low risk, of AMI. If so, what is a reasonable turnaround time for community samples — three hours?
At the other extreme is rigorous pursuit of fast turnaround times to meet the apparent clinical need in the community, probably with the help of point-of-care testing, although there are questions about the performance of point-of-care troponin assays.
For example, when samples are taken late in the afternoon, results might not be available until after clinic hours. In the event that a doctor cannot be found to take the result, which is not uncommon in our experience, laboratory staff usually pathologists phone patients directly and advise that hospitalisation is the safest course of action.
But when a patient cannot be contacted, laboratory staff face a dilemma: We are aware of anecdotal cases in which after-hours notifications of high troponin levels to patients at home have probably contributed to their early survival — but this raises the question of whether such patients are better served by referral to hospital in the first instance. A published coroner's case touches on these important issues for both GPs and pathologists. Positive troponin test results usually change the course of management, but the time frame in which the result becomes available must be balanced against the risk of delay in diagnosis and therapy.
A troponin test should not be requested unless a GP is certain that a robust process is in place by which they can be contacted, day or night, if the result is positive. There is an obvious need for further education, research and inclusion of this topic in future clinical guidelines.
Our suggestions for using, or not using, troponin tests in general practice are summarised in the Box.