Cardiac biomarkers of acute coronary syndrome: from history to high-sensitivity cardiac troponin

Pankaj Garg, Paul Morris, Asma Lina Fazlanie, Sethumadhavan Vijayan, Balazs Dancso, Amardeep Ghosh Dastidar, Sven Plein, Christian Mueller, Philip Haaf, Pankaj Garg, Paul Morris, Asma Lina Fazlanie, Sethumadhavan Vijayan, Balazs Dancso, Amardeep Ghosh Dastidar, Sven Plein, Christian Mueller, Philip Haaf

Abstract

The role of cardiac troponins as diagnostic biomarkers of myocardial injury in the context of acute coronary syndrome (ACS) is well established. Since the initial 1st-generation assays, 5th-generation high-sensitivity cardiac troponin (hs-cTn) assays have been developed, and are now widely used. However, its clinical adoption preceded guidelines and even best practice evidence. This review summarizes the history of cardiac biomarkers with particular emphasis on hs-cTn. We aim to provide insights into using hs-cTn as a quantitative marker of cardiomyocyte injury to help in the differential diagnosis of coronary versus non-coronary cardiac diseases. We also review the recent evidence and guidelines of using hs-cTn in suspected ACS.

Keywords: Acute coronary syndrome; Cardiac biomarkers; High-sensitivity cardiac troponin.

Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of human and animal rights

There is no need to cite/report any Ethical Statement.

Informed consent

This is a review and no patients have been involved in this research study.

Funding

Dr. Haaf has received research grants from the Swiss National Science Foundation (P3SMP3-155326). All other authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
Timeline of the development of cardiac biomarkers for the diagnosis of acute myocardial infarction
Fig. 2
Fig. 2
Detection range of different troponin assays. The green bars represent the normal turnover range of troponin in healthy individuals. With the onset of myocardial infarction, a slight rise in cardiac troponin can be seen that represents either ischemia-induced release of cytosolic troponin or micro-necrosis (orange-bars). Between 2 and 6 h, a steep increase in levels of cardiac troponin can be seen that represents extensive myocardial necrosis (red-bars). Only this major increase of cardiac troponin can be detected by first to fourth generation troponin assays. hs-cTn (5th generation troponin assay) can also detect lower levels of troponin including ischemia/micro-necrosis and even the normal turnover
Fig. 3
Fig. 3
High-sensitivity cardiac troponin as a quantitative marker. AMI acute myocardial infarction, CAD coronary artery disease, CHF congestive heart failure, HI healthy individual, LVH left ventricular hypertrophy, PE pulmonary embolus, SAB Staphylococcus aureus bacteraemia. The lower the level of hs-cTn, the higher the negative predictive value (NPV) for the presence of AMI. The higher the level of hs-cTn, the higher the positive predictive value (PPV) for the presence of AMI. Levels just above the 99th percentile have a low PPV for AM
Fig. 4
Fig. 4
Algorithm for rapid early rule-in and rule-out of acute myocardial infarction with high-sensitivity cardiac troponin assays, adapted from [40]. It is generally recommended to use the 3-h algorithm. In cases of high pre-test probability for NSTEMI and if chest pain onset >3 h, a 1-h algorithm has now been proposed with assay-specific hs-cTn cutoff levels. Any algorithm should always be used in conjunction with clinical assessment and 12-lead ECG. Repeat blood sampling may be deemed necessary in cases of ongoing or recurrent chest pain. GRACE “Global Registry of Acute Coronary Events score”, hs-cTn high-sensitivity cardiac troponin, ULN upper limit of normal, 99th percentile of healthy controls, D change is dependent on assay, DD differential diagnosis

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