Troponin T or troponin I and Why ?! In a suspected patient of ACS , if you have one option , either to select Troponin-I or Troponin-T , which one do you prefer ?

Written by : Dr.Nabil Paktin,MD.,F.A.C.C.

With the emergence of cardiac troponin T (cTn T) in the late 1980s and troponin I (cTn I) in the early 1990s, the diagnosis of Myocardial Infarction become easy .

Figure 1 

The mechanism by which cTnI and cTnT are released into circulation has not been well  elucidated but posssibilites suggested include normal turnover of myocardial cells , apoptosis , cellular release of cTn degradation products , increased cellular wall  permeability , formation and release of membranous blebs and myocyte necrosis .Although assays for cardiac troponin T (cTnT) and cardiac troponin I (cTnI) exhibit similar clinical performance in patients with acute coronary syndromes for diagnosis and risk stratification, there are differences in the release and clearance of these proteins from damaged myocytes.

          In certain situations , troponin I and Troponin T results may differ , and therefore these two assays cannot be used interchangeably .

1- After Cardiac surgery , significantly different results can be expected from these two assays , with troponin I reaching much higher levels than Troponin T .

2-Different epitopes/antibody recognition sites will result in difference in the detection of complexes and degradation products as well as Differences in phosphorylation , reduction and oxidation is also there .

3- Heparinized plasma samples allow more rapid analysis than serum samples, but preliminary studies showed lower cardiac troponin T (cTnT) results in plasma. negatively charged polyanions on heparin bind to positively charged troponins. To the best of our knowledge, loss of troponin T in heparin sampling tubes has not previously been published. The early phase of myocardial damage, troponin T occurs mainly as a “free cytosolic” form; in the later phase, it occurs in the “structurally bound” form and fragments . Troponin I is primarily released into plasma as a binary complex with troponin C and later occurs as a distribution of a variety of forms . We conclude that heparin decreases the measured concentrations of cardiac troponins, probably by binding to troponins and reducing their immunoreactivities. The magnitude of the decrease depends on the distribution of different troponin forms in circulation during and after myocardial damage and on analytical antibodies used in different troponin assays.Figure 1 .

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4- A review of the biochemistry of these proteins may provide insights as to the nature of these differences. Cardiac troponin T has a higher overall tissue concentration and free cytoplasmic concentrations than cTnI, and appears in blood of patients with acute myocardial infarction as a mixture of complexed (cTnT-I-C) and free cTnT. Cardiac troponin I is more hydrophobic and appears in blood predominately in the binary complex (I-C) form, with smaller amounts of the ternary (T-I-C) complex. Degradation of the complex will lead to faster clearance of the protein.


5-. One standardized assay exists for troponin T, while multiple assays are available for troponin I; each has a different cutoff value, as these assays target distinct epitopes, but , in the term of sensitivity and specificity both are almost the same , but Troponin I is higher sensitive compare to Troponin T relatively in all type of assays . Troponin I is slightly more reliable . 
However, new assays provided higher sensitivity , although the increasing sensitivity of cTn assays lowers the number of potentially missed ACS diagnosis , if presents a diagnostic challenge because the giants in diagnostic sensitivity have inevitably come with a decrease in specificity at all .

6-Troponin T is more elevated than troponin I in patients with chronic kidney disease, even at baseline. Although the exact reason for this is unknown, it has been postulated to result from a higher molecular weight of troponin T (resulting in a delayed clearance from the kidneys) as well as defect in kidney to not filter well. Accordingly, the disadvantage claimed by cardiologists for troponin T may turn into an advantage for nephrologists.

7-Recent reports on mismatches of cTnI and cTnT in patients with renal failure and myopathy without other evidence for myocardial injury suggest that cTnT could be reexpressed similar to CKMB and LDH-1 in chronically damaged human skeletal muscle. In contrast to cTnT, CKMB, and LDH-1, cTnI is not expressed in skeletal muscle during fetal development. So far, an increase in cTnI has been reported only after myocardial damage. Recent reports on increased cTnT in patients with renal failure or myopathy without evidence of myocardial injury and undetectable cTnI suggest that cTnT could be reexpressed similar to CKMB and LDH-1 in chronically damaged human skeletal muscle. Therefore, cTnI is probably the most heart-specific marker.

8- In general, for troponin T, the blood sample should not be frozen or refrigerated immediately, and it can be stored at room temperature for up to 8 hours for analyses.

9- However the third universal definition of Myocardial Infarction defined the myocardial infarction according to cTn ; one value above than 99 percentile URL with coefficient variation (CV) of less than 10% , and the demonstration of a rise and/or fall pattern of cTn. But , in this definition they couldn’t  further cleared the definition of rise and/or fall pattern , as per expert opinions and evidence-based articles it is shown there should be a typical and fast rise and fall of cTn from baseline , therefore cTnI having the faster rise and fall rather than cTnT in the term of emergency decision making . Release Kinetics of cardiac troponin after AMI are similar but troponin I returns to normal slightly earlier than Troponin T .
cTnI and cTnT usually peak in parallel except for patients without reperfusion in whom cTnI peaks about 1 day and cTnT approximately 3-4 days after onset of AMI. Both stay increased for at least 4-5 days. cTnT tends to stay increased longer than cTnI. Because the sensitivities of cTnI and cTnT for myocardial injury are comparable, their specificities are the main topic of current debate.

10- Recent researches shown that there is a Cardiac troponin T quantitative assay failure as a result  of antibody interference .It is proposed that the interference resulting in assay failure may not be because of a heterophile antibody, but rather a result of a circulating autoantibody to cardiac  troponin T, which may compete with antibody assay reagents for binding sites.

Figure 2 

11-Troponins are mainly bound to the myofibrils, although 6–8% of cTnT and 2.8–4.1% of cTnI is cytosolic. This affects release kinetics. There is rapid early release of cytosolic cTnT after ischaemic injury, followed by more prolonged release of myofibrillar troponin, resulting in a biphasic release pattern. As cTnI has a smaller cytosolic pool, release is likely to be monophasic.Please See Figure 1 . 


12- Troponins can rise due to ischemia without necrosis  also , about 94% of troponins are attached to the contractile units and this is released when myocyte dies . there is also another mechanism which release the cardiac troponins without necrosis ; free cytosolic about 6% of total can get released during episodes of severe ischemia . In this mechanism myocyte cell membrane is responsible due to being leaky and porous due to defective cell membrane integrity . It is believed that hypoxia triggers acute shortage of ATPs which are vital for membrane integrity .
Therefore, when there is large amount cTnT in free cytosolic than cTnI , it will be more released due to severe ischemic events compare to cTnI , this is why the cTnI is slightly typical of  necrosis more than  in ischemia relatively . ( Please see figure 1)