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New sensitive markers to detect myocardial infarction

By Professor Christian Müller

New biomarkers significantly improve the early detection of acute myocardial infarction (AMI). Recent studies reveal a novel and promising way for doctors to conclusively ensure that a patient is having or not having an AMI in a timely and accurate manner saving time and money.

In the assessment of patients presenting with chest pain and suspected AMI doctors rely on detailed patient assessment, the ECG, and the measurement of cardiac troponins (specific markers for dying cells in the heart). AMI is the cause of death in more persons worldwide than any other disease. With effective treatment within our grasp, accurate and rapid diagnosis is of major medical and economic importance.

With the development of blood tests depicting either cardiac troponin I or cardiac troponin T, the only current biomarkers thought to be unique to the heart, the diagnosis of AMI has been veritably revolutionised. In a patient presenting with chest pain, a rise in cardiac troponin has become a mandatory feature for the clinical diagnosis of AMI. Unfortunately, current cardiac troponin assays have one major limitation in common with their predecessor (CK-MB): it takes 3 hours after symptom onset until cardiac troponin becomes detectable. This is a major problem for doctors and causes diagnostic uncertainty particularly in patients presenting within the first hours from chest pain onset.

Recently, data from large multicenter studies have become available that demonstrate for the first time the impact of two novel biomarkers and therefore two novel approaches in the early diagnosis of AMI: sensitive cardiac troponin assays and copeptin, a marker of endogenous stress, in combination with standard cardiac troponin. Both approaches seem to largely overcome the sensitivity deficit of current standard cardiac troponin.

The more sensitive the cardiac troponin assay used, the smaller the number of dying myocardial cells necessary for this signal to be detected. Recent studies have clearly shown that sensitive cardiac troponin assays have a significantly higher diagnostic accuracy for the diagnosis of AMI and enable doctors to detect AMI already at presentation to the emergency department in the vast majority of patients.

More rapid diagnosis of AMI may reduce complications by allowing for earlier revascularization, earlier transfer to the coronary care unit, and earlier initiation of evidence-based treatment for AMI. In addition, the sensitive cardiac troponin assays may make it possible to reliably rule out the diagnosis of AMI in many patients on the basis of the initial measurement. The negative predictive value of the 99th percentile of the sensitive cardiac troponin assays, used as a single variable, was 97 to 99%. When sensitive cardiac troponin assays are used in conjunction with a clinical assessment and ECG, they will substantially reduce the percentage of patients in whom the diagnosis is uncertain after the first cardiac troponin measurement and for whom continuous ECG monitoring and serial blood sampling is necessary. The cost savings associated with this increase in early diagnostic accuracy might be substantial.

Similar findings were reported for the combination of copeptin and standard cardiac troponin. Copeptin, the C-terminal part of the vasopressin prohormone, is a marker of acute endogenous stress. If a patient suffering chest pains tested negative at presentation for both standard cardiac troponin and copeptin, which was the case in two-thirds of all patients studied, then there was a 99% probability that the patient was not having AMI, the study found. Only in the remaining minority of patients testing positive for either marker or both, would it be necessary to go the usual route of staying in the emergency room, monitoring and retesting a few hours later.

By looking at the copeptin levels in blood as a marker of acute endogenous stress, Tobias Reichlin, M.D., and co-workers from the Department of Internal Medicine, University Hospital Basel, Switzerland, sought to determine the incremental value of copeptin for a rapid rule out of AMI. Since the onset of chest pain associated with AMI is an enormous stress for the patient, copeptin levels were highest in patients presenting very early after the onset of symptoms.

Jacquelline Partarrieu | EurekAlert!
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