Dear Lifelong Learners and Readers of the TR POD:
During one of the meetings on my admin rotation, this interesting question arose:
should we also be ordering serum creatinine kinase muscle/brain (CKMB) level on our ACS rule out patients?
This derives from Cardiology’s concern that there are too many patients with elevated troponin with catheterizations that were not significant for
TRUE
acute symptomatic coronary artery stenosis.
In the absence of a STEMI or STEMI equivalent, we rely on serum biomarkers to support our hypothesis that the patient has myocardial ischemia.
Over the recent history of medicine, biomarkers supporting the diagnosis of myocardial ischemia have become increasingly sensitive. Which is to say, if the biomarker is negative, the condition you are testing for is more likely to be absent.
As the sensitivity increases, the probability with you can safely say a disease is not present also increases because the number of false negatives for that particular test decreases. However, this comes at the cost of an increasing number of false positives. The main problem that is highlighted in the graph below is that as we increase sensitivity, we increase the number of false positives, assuming a normal distribution.
For those of you who want to review biostatistics (especially interns); take a look:
https://lifeinthefastlane.com/ccc/diagnostic-tests-in-research/
Below, is a graph showing different rises of biomarkers during a proven myocardial infarction (MI). Note that AST is not included in this graph, but it is very similar to the total CK line as per my review of the literature.
As emergency providers, we are trying to rule out acute coronary syndrome (ACS) and suspicion for coronary artery disease (CAD). We aim to get into the nitty gritty of the statistics by which we practice: from both a historical perspective as well as a perspective of the clinician practicing today.
In the 50’s snd 60’s, the mainstay lab test was AST and CPK.
Sensitivity: 35%
Specificity: 58%
The above link offers a clinically derived calculator (non-validated) to predict the severity of stenosis. Presumably, the higher the AST, the higher the stenosis.
So back in the day: if a patient had typical chest pain symptoms and elevate AST/CPK, they may have gone to the cath lab. Today, that would never fly, but back then it was all they had.
In the 70’s doctors used the slightly more sensitive CKMB.
Sensitivity: 65%
Specificity: 46%
In the 90’s there was low sensitivity cardiac-troponin which was used in combo with CKMB.
Sensitivity: 67%
Specificity: 74%
In the 2000’s, next generation cardiac troponin I and T assays were even more sensitive.
Sensitivity: 89%
Specificity: 79%
***the reason for this low-ish sensitivity is due to the delay in elevation of troponin levels compared to other markers. The test is actually 99% sensitive when enough time has passed for the troponin to be elevated, given the appropriate clinical picture.
Some institutions have
high sensitivity cardiac troponin
;
we don’t.
But FYI: Sensitivity is even higher and the specificity is lower. Because we don’t use this assay, we will not get into the specifics of this assay.
Ironically, the newer “high sensitivity assays” that are available in Europe may decrease the false positive rate
. This is because there is higher resolution at the 99th percentile cut off point; which is to say: what we see as equivocal/borderline-positive troponin with our current assay may in fact be negative. Even though marketed as high sensitivity, that is actually not what the assay is in comparison to our current tests. What high sensitivity troponin means is more accuracy in defining non-zero troponin levels that are not positive for true ACS.
Causes of elevated troponin that are not due to ACS as a result of critical CAD are broad: sepsis, stroke, pulmonary embolism, CHF, renal failure, myocarditis and pericarditis.
So, a mild to moderately elevated troponin level in the setting of another disease process does not warrant a hard push to the cath lab unless it is indicated by the patient’s particular presentation.
To come back full circle to the initial question:
is CKMB, myoglobin, or CK indicated?
The answer is complicated. It should be case specific. Any cardiac chest pain with recent onset (less than 4 hours) that is concerning for MI, I would add on myoglobin and CKMB. This could be especially important if you are dealing with unstable angina with intermittent chest pain. If the myoglobin is elevated and the patient has chest pain with a normal troponin and a non-ischemic appearing EKG, I would use that elevated myoglobin and active chest pain to get a prompt cardiology evaluation. In these cases, the troponin becomes elevated later.
Moreover, our cardiology colleagues are seeking more data to push them one way or another in the absence of slam-dunk EKG findings. After reviewing the literature, in my opinion:
our troponin assay should be sufficient with serial testing
UNLESS
the patient has had recent MI, PCI, a comorbid condition that can elevate the troponin level, or
chest pain that started
minutes ago
. If they have a comorbid condition, CK, CKMB, and Myoglobin may help differentiate the cause of the elevated troponin. While none of these tests will be a gold standard like a cardiac catheterization, the results can certainly help our Cardiology colleagues who will undoubtedly be consulted as inpatients for “NSTEMI”. For example, an elevated troponin with a normal myoglobin might be
very reassuring.
No test is perfect.
There is always some degree of uncertainty regarding the significance of a result.
If they have chest pain and it is early but no STEMI or STEMI equivalents on EKG, get that CKMB and Myoglobin.
They’re cheap tests
. If you get a patient with an elevated myoglobin, non-ischemic EKG, but has active chest pain, that is one more argument that you have to advocate for a cardiac catheterization.
TR,
W
References:
https://path.upmc.edu/cases/case178/dx.html
http://www.ijmedicine.com/index.php/ijam/article/viewFile/317/287
https://step1.medbullets.com/stats/101006/2x2-tables-sn-sp-ppv-npv-or-rr
https://www.slideshare.net/cksheng74/sensitivity-specificity-and-likelihood-ratios
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