cardiac markers (troponin)
troponin
- see also troponin
- troponin has now replaced CK-MB as the main marker for acute coronary events
- there is still debate as to the appropriate timing of troponin levels - many use 4 hourly levels up to 12 hours post-onset of most severe pain episode, whilst others are happy to reduce hospital length of stay by accepting a 6-8 hour level from onset.
- a normal troponin DOES NOT necessarily mean the patient is not at risk of cardiac mortality within 30 days, particularly if the patient has high risk factors, but in the absence of these risk factors, it is generally assumed the patient will be safe for discharge and early outpatient cardiac stress testing and follow up.
- unfortunately, elevated troponin levels may occur in conditions other than acute coronary syndromes but in these cases are generally associated with severity of illness:
- chronic elevation:
- chronic myocardial ischaemia
- acute ischaemia or cardiac strain but not an acute coronary syndrome
- extreme exertion
hsTnT
- hsTNT or the 4th generation high-sensitivity troponin T assay (introduced in many labs in 2011) is even more sensitive but less specific for acute coronary events
- usually have a limit of detection of 3 ng/L of Troponin T and an “abnormal” cutoff being > 14 ng/L.
- indeed many normal people (particularly those doing extreme exertion such as marathon running) may have raised levels
- this has increased the complexity of interpretation of this test.
- this test is likely to double the number of patients with a positive troponin with implications for hospital resourcing to manage the false positives which include:
- renal failure, cardiac failure, pulmonary embolism, myocarditis, pericarditis, hypertrophic cardiomyopathy, tachyarrhythmia, bradyarrhythmia, cardiac procedures (surgery, pacing, ablation), cardiac infiltrative diseases, cardiac trauma, aortic dissection, stroke or subarachnoid haemorrhage, severe respiratory failure, severe sepsis, severe burns and extreme exertion.
- for most false positives the serial measurements should be similar unless the cause is an acute one in which case you can expect a false positive rising serial level.
- patients with a chronic steady raised hs-TNT may have chronic stable coronary disease and these patients are at increased risk of future heart failure and CVD mortality.
- the decreased specificity suggests that this test should not be done unless there is a good indication otherwise one will be left having to deal with a significant number of “false positives” as is the current situation with the D-Dimer test for PE. Unfortunately, having a good indication may also miss many acute coronary syndromes as up to 50% of all AMIs have atypical presentations.
- serial testing is needed to determine the clinical significance of the test but this has several considerations which need to be determined:
- what is a significant change in level (“delta”)
- is the change in troponin just within physiologic sampling or lab error margins?
- is a certain percentage change more specific for myocardial necrosis?
- a significant change is generally regarded as being > 50% above the baseline, or the level is >= 99th centile (Heart Foundation 2011 Guidelines addendum)
- what is the optimum timing of blood sampling:
- probably should be at least 2-3 hours apart and the one being at least 6 hours after onset of symptoms (although in practice many do a sample on arrival in ED as well)
- should we be looking at the measured troponin half-life?
- “ischaemic elevation” is associated with a shorter half-life than myocardial necrosis
| serial hsTNT result | DDx |
|---|---|
| stable and normal levels | no myocardial necrosis but perhaps too early or late to show a change |
| stable and elevated levels | plateau phase of ACS or chronic elevation - may need a 3rd sample |
| rising but with normal levels | physiologic change |
| rising and elevated levels | acute ischaemia or infarction |
| falling but with normal levels | physiologic change |
| falling and elevated levels | acute ischaemia or infarction |
CK-MB
- raised creatinine kinase (CK) levels can occur from any injury to any type of muscle cell including skeletal muscle (eg. even after an IM injection it is released, or in crush injuries when very high levels are suggestive of rhabdomyolysis and risk of renal failure if not managed)
- CK-MB is the isoenzyme released primarily from cardiac muscle and for many years was used as the sole indicator of myocardial infarction.
- after an infarction, CK-MB rises above normal levels at 4-6hrs, peaking at ~24 hours and falling back to normal levels by ~72hrs.
- a further rise once it has started falling suggests re-infarction.
- CK-MB may still rise after skeletal muscle injury and to help differentiate this the ratio of CK-MB to CK of greater than 5 indicated a cardiac source while a ratio less than 3 indicated a skeletal source, however, use of this index does decrease the sensitivity for cardiac events.
- CK-MB was replaced by troponin as a raised troponin was a much more sensitive marker for cardiac ischaemia.