Troponin T, High Sensitive

Performed in Chemistry

TROPTHS

5th generation

Green LiHep, Plasma

None

Samples stabilized with azide
Moderately or grossly hemolyzed

Daily, Sunday through Saturday

Less than 4 hours

Troponin T (TnT) is a component of the contractile apparatus of the striated musculature. Although the function of TnT is the same in all striated muscles, the cardiac isoform of TnT originating exclusively from the myocardium (cardiac TnT, molecular weight 39.7 kDa) clearly differs from skeletal muscle TnT. As a result of its high tissue‑specificity, cardiac troponin T (cTnT) is a cardio‑specific, highly sensitive marker for myocardial damage. Cardiac troponin T increases rapidly (i.e. can be detected within 1 hour if using high‑sensitivity assays)1 after acute myocardial infarction (AMI) and may persist up to 2 weeks thereafter.2,3 In contrast to ST‑elevation myocardial infarction (STEMI), the diagnosis of non‑ST elevation myocardial infarction (NSTEMI) relies heavily upon elevated cardiac troponin (cTn) concentrations in the appropriate clinical context. The Third Universal Definition of Myocardial Infarction (MI) has confirmed cTn as the biomarker of choice.4 Diagnosis of MI is made with acute changes in cTn concentrations with at least one serial sample above the 99th percentile upper reference limit (URL), taken together with evidence of myocardial ischemia (symptoms, electrocardiogram (ECG) changes or imaging results). Various guidelines and publications recommend the optimal imprecision (coefficient of variation) of cTn assays at the 99th percentile upper reference limit be less than or equal to 10 %.1,4,5,6,7 The 99th percentile upper reference limit is derived from a reference control group of normal, non‑diseased individuals.4,7,8 Several guidelines and research activities recognize that improved analytical sensitivity of cTn assays over the last several years has allowed for detection of other etiologies. Chronic cTn elevations can be detected in clinically stable patients such as patients with ischemic or non‑ischemic heart failure,9,10 patients with different forms of cardiomyopathy,11 renal failure,12,13,14,15,16,17,18 sepsis19 and diabetes.20 Elevated concentrations of cTn can also occur in other clinical conditions such as myocarditis,21 heart contusion,22 pulmonary embolism23 and drug‑induced cardiotoxicity.24 To distinguish between acute and chronic cTn elevations, the Universal Definition of MI stresses the need for serial sampling to observe a rise and/or fall of cTn above the 99th percentile upper reference limit consistent with the clinical assessment, including ischemic symptoms and electrocardiographic changes.4 Troponin elevations may persist for up to 14 days or occasionally longer.4 Other diagnostic tests such as NT‑proBNP and CRP can complement the diagnostic and prognostic information of cTnT in different indications. The Elecsys Troponin T Gen 5 STAT assay employs two monoclonal antibodies specifically directed against human cardiac troponin T.25,26 The antibodies recognize two epitopes (amino acid position 125‑131 and 136‑147) located in the central part of the cardiac troponin T protein, which consists of 288 amino acids. The Elecsys Troponin T Gen 5 STAT calibrators (CalSet Troponin T Gen 5 STAT) contain recombinant human cardiac troponin T (rec. hcTnT). The rec. hcTnT is isolated from cell culture of E. coli BL21 containing a pET vector with human cardiac troponin T isoform 3 gene. After fermentation, the cells are disrupted by sonication and rec. hcTnT is purified by ion exchange chromatography. Purified rec. hcTnT is further characterized by SDS PAGE, Western blotting, immunological activity, and protein content.27 By current universal definition of the disease (AMI), the 99th percentile URL should be used as a diagnostic cutoff of AMI,4 and is endorsed by major local guidelines.1,7,28 Yet, the International Federation of Clinical Chemistry (IFCC) recently observed that only 11 out of 31 of contemporary troponin tests can measure the 99th percentile URL with adequate precision (≤ 10 % CV at the cutoff) and therefore many tests are used with higher cutoffs (such as their analytical 10 % CV).8 Higher cutoffs produce higher estimates of clinical specificity and positive predictive value (PPV), but tend to underestimate clinical sensitivity and negative predictive value (NPV).29 When switching to the Elecsys Troponin T Gen 5 STAT assay, users should be aware that the guideline compliant test using the 99th percentile URL as a diagnostic cutoff, can lead to a relative increase in the diagnosis of acute MIs compared to contemporary assays using other, often higher cutoffs.1,30,31,32