The utility of high sensitive troponins in early diagnosis or rule out of AMI
Prof Dr Mehmet Ağırbaşlı
Department of Cardiology
Medeniyet University
School of Medicine
Istanbul, Turkey
magirbasli@gmail.com

 

Chest pain is the most common reason for emergency hospital admissions. Recent advances in diagnostic technology have improved the care significantly. There has been significant and recent progress in our approach to the patients with chest pain in emergency settings. Until recently, our abilities to diagnose acute coronary syndromes (ACS) were limited and patients were required prolonged evaluations lasting for 12-24 hours. Recent developments in high-sensitivity cardiac troponins (hs-cTn) and their potential to predict outcomes after myocardial infarction have been received in the global emergency care and cardiology communities with great interest  (1).

The term “high sensitivity” is defined as  2 analytical criteria need to be met (2).

First, the % CV at the 99th percentile upper reference limit (URL) should be 10%. Second, measurable concentrations should be attainable at a concentration at or above the assay’s level of detection (LoD) for 50% of healthy individuals (2).

The development of hs-cTn assays drastically changed the approach to early diagnosis of patients with chest pain. Compared to conventional cTn assays, hs-cTn assays have the potential to improve analytical sensitivity and precision. For instance, in a large study of 87,879 patients with a first MI, the use of high-sensitivity cardiac troponin T (hs-cTnT) was associated with an increased incidence of myocardial infarction (MI), and reduced risk of reinfarction compared with those diagnosed using conventional troponins (cTn) (3). Thus the introduction of the hs-cTnT assays led to a reduced risk of reinfarction.

Yet, analytic and preanalytic issues remain to be discussed in the use of the hs-cTnT in early diagnosis or rule out of ACS. Laboratory Medicine Practice Guidelines (LMPG) on cardiac markers of the National Academy of Clinical Biochemistry (NACB), and the American Association for Clinical Chemistry (AACC) Academy, published expert opinion statements as there is insufficient evidence regarding some of the important issues related to the the utility of hs-cTnT in early diagnosis or rule out of ACS (4, 5).

These recommendations implicate that there are numerous analytic testing issues that must be addressed to optimize the safety and effectiveness of cardiac troponin (cTn) in clinical practice. The most common issues that confound laboratory blood tests remain to be preanalytic. Clinicians are needed to be educated to recognize these issues.

Third Universal Definition of MI includes a decision point for all cTn assays at the 99th percentile upper reference limit (URL) from the distribution of a reference population (6).

Quality monitoring of cTn assays over time and utilizing quality control (QC) materials with concentrations higher than the 99th percentile have created a quality gap at or below the 99th percentile for the novel hs-cTnT assays.

Hs-cTnT assay uses the 99th percentile value for healthy controls as the decision limit for MI from the distribution of a reference population. There are gender and population related differences in reference intervals for hs-cTnT and hscTnI. Gender and population spesific cut off levels for hs-cTn may not be readily available for every population. Yet, population and gender specific cut off points may confer a clinical advantage of using sex-specific 99th percentiles. According to the Clinical Laboratory Practice Recommendations for the Use of CardiacTroponin in Acute Coronary Syndrome, the Academy of the American Association for Clinical Chemistry has implemented the use of 99th percentile concentrations according to sex-specific cutoffs for hs-cTn assays (4, 5).

In conclusion, several elements, in the history, physical examination, ECG,  and cardiac troponin concentrations integrate to guide clinical decision making in the evaluation of patients for ACS. The recent advances in hs-cTn promiss a tremendous future potential to further improve care while reducing unnecessary healthcare resource utilization. Addressing pre-analytical and analytical challenges may help to safeguard healthcare resources, which is vital given the increasing cost of care for ACS.

 References

  1. Body R., Mueller C., Giannitsis E. The use of very low concentrations of high-sensitivity troponin T to rule out acute myocardial infarction using a single blood test. Acad Emerg Med. 2016 Sep;23(9):1004–1013. [PubMed]
  2. Apple FS, Jaffe AS, Collinson P, Mockel M, OrdonezLlanos J, Lindahl B, et al. on behalf of the International Federation of Clinical Chemistry (IFCC) Task Force on Clinical Applications of Cardiac Bio-Markers. IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays. Clin Biochem 2015;48:201–3
  3. Odqvist M, Andersson PO, Tygesen H, Eggers KM, Holzmann MJ. High-sensitivity troponins and outcomes after myocardial infarction. JACC 2018; 71: 2616-24.
  4. Wu AHB, Christenson RH, Greene DN, Jaffe AS, Kavsak PA, Ordonez-Llanos J, Apple FS.Clinical laboratory practice recommendations for the use of cardiac troponin in acute coronary syndrome: expert opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on ClinicalApplications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry and Laboratory Medicine. Clinical Chemistry 2018; 64: 645-55.
  5. Apple FS, Jaffe AS, Collinson P, Mockel M, Ordonez-Llanos J, Lindahl B, et al. onbehalf of the International Federation of Clinical Chemistry (IFCC) Task Force on Clinical Applications of Cardiac Bio-Markers. IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays. ClinBiochem 2015;48:201–3.
  6. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Joint ESC/ACCF/AHA/WHF Task Force for Universal Definition of Myocardial İnfarction. Third universal definition of myocardial infarction. Circulation 2012; 126: 2020-35.