Conversations in Cardiology: The Push for High-Sensitivity Troponin

Morton KernMorton Kern, MD, of VA Long Beach Healthcare System and University of California, Irvine, often engages his colleagues via email in brief, informal dialogue on clinically relevant topics in interventional cardiology. With permission from the participants, TCTMD presents their conversations for the benefit of the cardiology community. Your feedback is welcome—feel free to comment at the bottom of the page.


Samuel Butman, MD (Heart & Vascular Center of Northern Arizona, Cottonwood), asks:

I have a question regarding high-sensitivity troponin T/I, maybe to ask the group?

Apparently there are plans afoot to go to a high-sensitivity troponin T assay soon where I practice, and we are having a meeting later today to discuss.

What is the sense of the reality after the switch regarding more or less admits, procedures, and MI over- and/or underdiagnoses relative to whatever time is saved in the ED by the quicker triage with the high-sensitivity assay?

Kern replies:

My thoughts on the question: "What is the value of high-sensitivity-troponin?"

Honestly, I don't know and, moreover, I'm not sure it will make a difference. Right now we at the VA are often bombed with “trop” note requirements to address every minor troponin elevation, related or not to a cardiac cause. I think high-sensitivity troponin assays will likely double our work and keep us in business. Is it better patient care? I doubt it.

My colleagues can share their view and temper my cynicism.

Keith Oldroyd, MBChB (Golden Jubilee National Hospital, Glasgow, Scotland), replies:

In Scotland, we have been using high-sensitivity troponin since around 2014-15 and Nick Mills from Edinburgh has led some significant research into its use. Paul Collinson, who has been heavily involved in the development and use of troponin in the UK, likes to say that troponin used to be a poor assay but a great test whereas now it is an incredibly sensitive assay but a lousy test. I tell the medical students that if a patient with CHD sneezes the high-sensitivity troponin goes up!!

Having said that, it is clearly an advance in terms of rapidly ruling out MI in patients presenting with chest pain and the protocol/cutoff values we use in Scotland have some slight advantages over that recommended in the European Society of Cardiology guideline (see here and here). We now also have a sex-specific normal range, which may address one aspect of underdiagnosis in women.

There are two big problems. Firstly, we see people with ongoing unstable angina inappropriately sent home from the ED because their troponin is negative. Secondly, we have seen an increase to almost epidemic proportions of patients admitted and referred for urgent cath because their troponin was elevated but in fact they never had an ACS in the first place (type 2 MI). That has always been an issue, but it’s a bigger problem with the high-sensitivity assays. Obviously both of these problems can be at least partly addressed by input from experienced clinical cardiologists, which in our system is not always available.

Gregg Stone, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), replies:

Another issue is the use of hs-troponins for post-PCI procedural assessment of type 4a MI. The 99th percentile of the URL is lower for these assays then their standard counterparts, which in some of our trials is increasing the rate of periprocedural MI—this would happen of course in clinical practice too if they are regularly assessed. Since the clinical impact of even standard troponins after PCI is not yet established (depending on the threshold related to the URL), this lower threshold for type 4a MI with high-sensitivity troponins adds even more uncertainty. Has anyone else experienced this issue either in the setting of leading clinical trials, or in clinical practice? 

Sunil Rao, MD (Duke University Medical Center, Durham, NC), replies:

We have definitely noticed this at Duke Clinical Research Institute. Adjudication is particularly challenging.

I thought that the FDA was going to provide some guidance on this, but have not seen anything from them on this recently.

Bonnie Weiner, MD (Saint Vincent Hospital, Worcester, MA), replies:

The clinical trials issue is accentuated in patients in gene therapy trials where direct injection into the myocardial is performed and in patients who have also undergone ablation procedures.  

James Blankenship, MD (Geisinger Medical Center, Danville, PA), replies:

It is interesting that also in our system the lab was the moving force behind high sensitivity troponin assays. If put to vote, the cardiologists would have voted "nay" to high-sensitivity troponin. 

Butman replies:

Oh my! What have I unleashed? Actually nothing but for those who have responded an understanding that they they/we are not alone.

What about the apparent silent majority who have not opined yet? High-sensitivity troponin T is a fine test that is too sensitive and not specific enough.

Herein lies the problem. It is fine for ER staff because it can be used to rule out or in an MI early or similarly result in either a hospitalist or cardiology consult early. So, is this really a good thing for everyone else who is impacted? And in saying this, I am including hospitals, insurers, taxpayers, and of course the many, many patients who will succumb to unnecessary testing for sure.

I'm just saying.

Neal Kleiman, MD (Houston Methodist Hospital, Texas), replies:

You make an excellent point. The test is really designed and tested for triage rather than for patient management.

Jeannie Yu, MD (VA Long Beach Healthcare System), replies:

Fascinating discussion, Dr. Kern.

There is a disconnect between the scientific rationale of a higher-sensitivity troponin and the practical implications of high-sensitivity cardiac troponin T (hs-cTnT).

I understand that the hs-cTnT is supposed to help allow early ER discharge within 1-3 hours of chest pain onset if the test comes back negative. How often will the hs-cTnT actually be negative and allow early discharge compared to how many people, for example, who came in for GI viral illness with nausea now have a positive hs-cTnT? In the VA population, it seems the odds would be highly skewed to positive enzymes of no ACS-related clinical significance favoring admission.

We know that the hs-cTnT is so sensitive that it is positive in a large number of stable, asymptomatic outpatients without any history of CVD or diabetes mellitus (ARIC study). Those people also get noncardiac illnesses that bring them to the ER, and now they will be admitted for a blood level that would not have been positive outside. Of course, we want to take care of these patients in modifying their risk factors, but not as an inpatient. So if your hs-cTnT goes up in patients just by having diabetes and other comorbid conditions, outside of obstructive CAD, that does not seem specific enough to use except as a rule-out test, but we know that the ER and hospitalists won't use it that way.

And it seems from the interventional comments, these patients are not getting any more caths than before. But if that's the case, then it is logical to suspect that those patients are likely receiving more noninvasive testing via treadmill, nuclear or cardiac CT angiography as a gatekeeper to the cath lab. Is all of this testing for hs-cTnT of otherwise unclear origin necessary? Is this truly in the best interests of the patient?

Perhaps one wonders why any provider (cardiologist or otherwise) would get an ischemic evaluation if the patient were not classically symptomatic? Yet if you have a patient with squirrelly symptoms (belly pain from unknown cause, vomiting from GI bug, pleuritic chest pain from pneumonia, etc) and now admitted with a "positive" troponin, do you feel comfortable discharging them with no further workup? I would wager most would not.

I am not actually against the hs-cTnT as a lab. I would vote for it to be much more clearly vetted and laid out in an algorithm in terms of use and interpretation by the professional societies in conjunction with the ER society and hospital medicine, so that it doesn't inadvertently lead to a huge increase in admissions and cardiac testing for unclear benefit. And if the onus is going to be on the individual provider to take the medical and legal risk of discharging a positive hs-cTnT from the ER, they will probably all be admitted and stress tested.

Kirk Garratt, MD (Christiana Care Health System, Newark, DE), replies:

We’re also looking at high-sensitivity troponin for our hospital system, but it’s being driven by me, not lab medicine (in fact, lab medicine is pushing back a bit because it means updating some machines). I’m keen for the reasons mentioned: much greater diagnostic accuracy that improves our ability to render appropriate, efficient care. The problem is that, as a more sensitive test, our previous coarse cutoff values aren’t suitable. We have to take age and gender into account, and be ready to interpret a value in the context of patient presentation. It’s more complicated, and although it doesn’t require a cardiologist, the noncardiologists will look to us for guidance on it for a while. I’d like to hear from some who’ve made the switch about how long it took for hospitalists, ED docs, and others to get comfortable with it. I’m convinced the juice is worth the squeeze: the studies on this suggest big benefits, mostly in being able to send home the horde of low-risk patients that occupy our observation beds. As the pressure rises to migrate work to outpatient settings, those observational beds get more valuable.

Butman replies:

Thanks Mort, and thank you to all who have taken the time to comment on this "better" test. Very helpful given that this was/is apparently uniquely being driven by the lab people and not clinicians in either the ED or cardiology, oddly enough.

Apparently the drive to do this was not for clinical reasons but for their assumption that the standard troponin test is likely not to be supported by the vendor in the not too distant future.

Tail leading the . . . ?

Note: A prior version of this conversation mistakenly attributed Yu’s comments to David Cohen, MD.