Understanding Troponin
To understand Troponin use in diagnosing Myocardial Infarction (MI) it is worth thinking about how MI used to be investigated before cardiac specific troponins were developed. We also need to understand how the test works and why there are different protocols in different hospitals as well as understand how it can be of use to us as clinicians.
We used to look at 2 different markers that would rise at different points and the combination would be what would suggest MI as a potential diagnosis. However, much more weight would be attributed to the clinical picture, and as such much more myocardial damage would be missed.
These markers were a CK rise within 24hrs of the event incident (ie the patient having chest pain) and then a much later rise in ALT and LDH from ischaemic liver injury in the 2-3 days after the event.
Now what is Troponin?
A fundamental protein in all skeletal and cardiac muscle
3 types (I,T and C)
Troponin wraps around actin with tropomyosin allowing Myosin binding when an action potential causes Calcium ion influx
Both Types I and T have cardiac specific variants
How does Troponin end up in the blood?
When there is any muscle damage the break down leads those proteins to be released into the blood stream
Our cardiac specific troponins are released when there is any damage to the heart muscle - this is seen in MI but also in any scenario where the heart muscle maybe stressed like arrythmia, hypoxia from another source other than MI or even particularly strenous exercise.
Levels of troponin in the blood peak over 12-24 hours and it is renally excreted.
Given that troponin is renally excreted our baseline levels maybe higher in patients with renal failure. However, we know that in the event of cardiac myocyte damage the level will peak within 12-24hr. We can distinguish between a high baseline level and damage by taking sequential blood samples to measure the level - when there has been acute damage, the level will continue to rise. This is often referred to as a Delta Change.
Typically following an MI the Troponin level will stay elevated for 10 days. This is dependent on the initial injury. A large STEMI may lead to a raised level for weeks, whilst a smaller injury may have complete clearance within 24hrs.
How are Troponins measured?
- Immunoassys with a signal attached to the antibodies (for example Trop T assays give off light when electicity passed through the sample giving a reading)
- Analytic sensitivity (reliability of detection at low levels) is different to Diagnostic Sensitivity
o Analytic sensitivity is around 90% on attendance to ED
The timing of troponin samples in clinical practice is based on analytic sensitivity. As in how long post event do we need to leave it to make sure we pick up any troponin rise. This is an ever improving technology and has seen the time for a troponin sample to be able to be used as a rule out drop from 24hrs to less than 3. This is dependent on the equipment in the lab and the sensitivity standards set locally.
- Variation in use of high sensitivity trops, most of the world does from the time of attendance not time of symptoms to increase the sensitivity of the trop. UK is different in that it uses time from event rather than presentation. Maybe this is related to cost savings and reducing admissions/time in hospital.
The application of troponin with Bayesian thinking
- If we did troponin on every patient that came through the doors some would be raised.
- But the results would be meaningless without the context. Have they all had MIs?
- So think of 2 different patients:
o A story of a 60m, obese, smoker with central chest pain
o 25f fever, hypotension, tachycardia dysuria and flank pain
o Now thinking about what the differential is. However both their trops could be around 100.
§ It is likely one has had an MI. the other is just demonstrating T2MI from sepsis. Possible direct cardiac damage or from renal injury
- Our intial assessment has given us the initial probability/suspicion/perception of their injury and then the test has been used to refine the process.
o But they have been used together to determine the most likely cause of the patient’s problems – this is the Bayesian Theorem
