Troponin Sensitivity Training

High-sensitivity troponins are finally here! The FDA has approved the first one for use in the United States. Now, articles like this are not for purely academic interest – except, well, for the likely very slow percolation of these assays into standard practice.

This is a sort of update from the Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) consortium. This consortium is intended to “advance the early diagnosis of [acute myocardial infarction]” – via use of these high-sensitivity assays for the benefit of their study sponsors, Abbott Laboratories et al. Regardless, this is one of those typical early rule-out studies evaluating the patients with possible acute coronary syndrome and symptoms onset within 12 hours. The assay performance was evaluated and compared in four different strategies: 0-hour limit of detection, 0-hour 99th percentile cut-off, and two 0/1-hour presentation and delta strategies.

And, of course, their rule-out strategies work great – they miss a handful of AMI, and even those (as documented by their accompanying table of missed AMI) are mostly tiny, did not undergo any revascularization procedure, and frequently did not receive clinical discharge diagnoses consistent with acute coronary syndrome. There was also a clear time-based element to their rule-out sensitivity, where patients with chest pain onset within two hours of presentation being more likely missed. But – and this is the same “but” you’ve heard so many times before – their sensitivity comes at the expense of specificity, and use of any of these assay strategies was effective at ruling out only half of all ED presentations. Interestingly, at least, their rule-out was durable – 30-day MACE was 0.1% or less, and the sole event was a non-cardiac death.

Is there truly any rush to adopt these assays? I would reasonably argue there must be value in the additive information provided regarding myocardial injury. This study and its algorithms, however, demonstrates there remains progress to be made in terms of clinical effectiveness – as obviously far greater than just 50% of ED presentations for chest pain ought be eligible for discharge.

“Direct Comparison of Four Very Early Rule-Out Strategies for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin I”

2 thoughts on “Troponin Sensitivity Training”

  1. Thanks for all you do distilling recent lit, Ryan. I’d like to offer a slightly different take on hs-Troponins take having used these assays for about 4 years north of the border.

    It’s probably unrealistic to expect that hs Troponins will offer much of an improvement in terms of sensitivity/miss rate–the miss rate in most North American and European EDs is already pretty low. The advantage to be gained is in terms of length of stay for patients undergoing workup. If even 50% of possible AMI patients can be ruled out within an hour or two compared to the 6-24h status quo with conventional troponins, that’s a substantial reduction in ED burden (not to mention the burden on patients). That’s been both the published and anecdotal experience from Canadian EDs that have been using hs Troponin assays.

    With respect to specificity, we need to keep in mind that these are rule-out algorithms, not rule-in algorithms. An important realization is that hs-Troponins are not binary tests: optimal utilization will require different rule-in and rule-out algorithms with different cutoffs. We’ll have to get used to thinking a bit harder to use these assays to their full potential.

    My biggest worry with 1hr algorithms validated for both hs-cTnT and hs-cTnI are that the 1-hour rule-out delta is pretty close to the variability/error of the assay itself, so there’s a potential for misses purely as a result of assay variability. It may be that 2- or 3-hour algorithms are more robust but that remains to be seen.

    1. I mostly agree – you can certainly design some sort of intelligent protocol for rule-out using these data and the different threshold and different time points and differing time of onset of symptoms – as well as the different factors associated with pretest likelihood of disease, as well.

      Binary use of troponin is obsolete – and probably binary definitions of AMI, as well, considering. Do these patients with small troponin elevations need to be investigated in the hospital? Are they at risk for malignant arrhythmia? An aspirin and a statin can be started without overnight hospitalization pending additional community follow-up, as appropriate. This is a complicated issue, and, yes, we need quick solutions in the ED – but protocolizing these things is unlikely to be the best value solution for all patients.

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