Category: Troponin

High-Sensitivity Troponin Dead End

Another article trying to work the unworkable – the balance between sensitivity and specificity.

From New Zealand, an attempt to evaluate the Roche Laboratories hsTnT assay in the interests of performing accelerated rule outs in the ED – looking at any combination of initial value, 2-hour value, delta between 0-2 hour value, etc.  And, essentially, any strategy you choose is wrong.
On one hand, you can get up to 91.4% specific for their gold  standard of AMI by requiring a hsTnT  >14 ng/L and a 20% delta change at 2 hours – but your sensitivity will drop to 72%.  Conversely, you can have sensitivity of 98.8% – which is the point of these hsTnT testing strategies – but your specificity drops to 56.4%.  Unless you’re doing something intelligent with all those false positives that isn’t harmful, expensive, or invasive, the costs of zero-miss are, once again, too high.
“High-sensitivity troponin T for early rule-out of myocardial infarction in recent onset chest pain”

Heart Fatty Acid Binding Protein

A nice comparison of the sensitivities and specificities of the various biomarkers for acute myocardial infarction at ~3.5 hours after symptom onset.  Each biomarker was set at the 95th or 99th percentile based on manufacturers definitions for their reference table, and then they also show ROC curves and calculate AUCs for each.

Essentially, none of the biomarkers is completely adequate for ruling out AMI given the constraints of their study.  Their best combination, for both sensitivity and specificity, is combining the heart fatty acid binding protein and the troponin – which they state provides an NPV of 95.6%, outperforming the “triple rule out” of troponin, CKMB, and myoglobin at 92.1%.  Interestingly, they also state that if they used clinical risk stratification, they could select a population in which HFAP and troponin together get up to 96.9% NPV…showing that regardless the resources we throw at the problem of “low risk chest pain”, it is an absolutely Quixotic quest to definitively rule out every MI in the Emergency Department.  3% of their “very low risk” population that was biomarker negative with the best sensitivity they could muster ended up ruling in for AMI during their subsequent hospital stay.  They only way we’re going to prevent healthcare from becoming bankrupt is increasing our levels of acceptable risk.

As a side note, this article gets the award for “best vs. least professional” title so far this year.

http://www.ncbi.nlm.nih.gov/pubmed/21561701

More Sensitive Troponin Assay Saves Lives?

These authors show us something very interesting about “negative” troponin testing in their prospective review.  Like my facility, they had an assay with a certain level of detectability.  I will say, though, that their assay detection level of 0.20 ng/mL is different than our assay, that goes down to 0.02 ng/mL.  But, basically, they implemented a new assay that was sensitive down to 0.05 ng/mL but didn’t tell their clinicians any of the newly detectable troponin numbers below 0.20, but they built a database of the cohort in that detectable-but-previously-undetectable range.  Then, they showed clinicians their new detectable numbers and let them do what they wished with it.  It turns out, the population with the 0.05 to 0.20 troponins had similar cardiac morbidity/mortality risk as their >0.20 troponin population – while the truly undetectable did much better over their 1-year follow-up.

Additionally, after the new threshold was introduced, clinicians treated the 0.05 to 0.20 more similarly to the >0.20 group with additional testing, cardiology consultation, and medications – and their outcomes improved 20%.

So, this study really makes you think what it means to have a “negative” troponin and wonder what the disposition and follow-up should be at different points.  At my institution, we’ve traditionally said 0.10 ng/mL is the cut-off for “positive”, and the lesser, yet still detectable troponins, are “negative”.  But, this study clearly suggests that a lot of the patients we’re labeling “negative” really need to have more aggressive treatment.  This study doesn’t tell us whether they need to be inpatient, or have expedited follow-up, or precisely how to manage them in order to improve their outcomes, but it suggests a lot of great new questions to ask regarding how to use the information we receive from our troponin assay.

http://www.ncbi.nlm.nih.gov/pubmed/21427373