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Letter to the Editor

hs-cTnI's True Intent

doi: 10.1097/01.EEM.0000558208.29337.37
Letter to the Editor

Editor:

I believe Rory Spiegel, MD, misinterpreted the study in his article, “Hoopla Aside, hs-cTnI is Not Catching Missed MIs.” (EMN 2019;41[2]:1; http://bit.ly/2Bv4FUd.) The high-sensitivity troponin I reclassified 1771 patients as acute MI (about 600 type 1) not identified by the contemporary assay (cTnI), and their ultimate outcome was not different from those not reclassified. (Lancet 2018;392[10151]:919; http://bit.ly/2Erob73.)

This makes it seem that the hs assay has no value, that it simply leads to more investigations without improving outcomes. The reason for this is not increased test sensitivity but the threshold used for the test's upper reference limit. It also ignores the intended value of the test: earlier MI rule in or out.

The definitions of normal v. increased for both assays are based on the 99th percentile of a normal population, which may result in varying cutpoints for normal. The upper reference limit must also be accompanied by a low coefficient of variation, which measures the reproducibility of the test and should not exceed 10% at the 99th percentile. Different labs have different CVs and URLs; the laboratories used in the study had a 10% CV at a relatively high URL of 40 and 50 ng/L, higher than it would be in many labs. The URL for the cTnI assay in our lab is 30 ng/L, and the CV is less than 10% at this value. The higher URL would result in the cTnI assay being less sensitive in the study than it would otherwise. The hs assay uses different thresholds for women (16 ng/L) and men (34 ng/L). This is likely why women were reclassified in the study more often.

These factors may account for the differences in reclassification. Data from the UTROPIA study, in which the URL for cTnI was 30 ng/L (hs-cTnI used 16 ng/L for women, 34 for men), showed fewer positive assays with the hs-cTnI than with the cTnI; that is, it resulted in fewer false-positives. (Am J Med 2017;130[12]:1431.)

It is also important to remember that high sensitivity means analytical, not clinical, sensitivity. All positives and negatives are determined arbitrarily by the 99th percentile, so the two assays cannot be different in the proportion of MIs identified except for the different thresholds used and the number of hours of serial troponins measured.

I like to call high-sensitivity assays high-precision assays because they can accurately quantify low levels of troponin, far below the 99th percentile cutpoint. This means that troponin changes at low levels can be detected to rule MI in or out earlier by using low thresholds or delta values. Small changes at low values are true changes. A single extremely low value, which can now be quantified, can all but rule out MI in patients with at least two hours of chest pain. (JAMA 2017;318[19]:1913; http://bit.ly/2MVSsMT.)

The Lancet study used values at six to 12 hours after symptom onset to diagnose myocardial injury. The cTnI is excellent and just as sensitive as hs assays at six to 12 hours after symptom onset. The use of these late measurements negated the value of the hs assay, which is that it helps in early diagnosis and rule out. It is true that the hs assays will not catch missed MIs, but that was never the intent.

Stephen W. Smith, MD

Minneapolis, MN

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