Get Ready For High-Sensitivity Troponin Assays

Allan Jaffe, MD; Rajiv Gulati, MD, PhD


December 08, 2016

Editorial Collaboration

Medscape &

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Rajiv Gulati, MD: Greetings. I'm Dr Rajiv Gulati, a cardiologist at Mayo Clinic in Rochester, Minnesota, and today I'm joined by Dr Allan Jaffe, who is a well-known expert in the field of biomarkers and heart disease. Today we'll be discussing high-sensitivity troponin assays and how we use them or how we will be using them. Welcome, Allan.

Allan Jaffe, MD: Pleasure to be here with you.

Dr Gulati: Allen, perhaps we can start by outlining: what is high-sensitivity troponin?

Dr Jaffe: There's a fair amount of confusion. Clearly, we're developing assays that are more and more sensitive. What has been proposed as the metric to use, albeit relatively arbitrarily, is that high-sensitivity assays should detect values in a large number of normal individuals—at least 50%. That's chosen as a surrogate for clinical sensitivity.

The problem with that is that some assays, [such as] the Roche high-sensitivity assay, do not meet that [standard] in [many] evaluations and yet clinically seem to have a lot more sensitivity for the detection of disease. So there is some degree of arbitrariness there, but most of the very high-sensitivity assays detect values in 80% to 100% of people, so it is very likely that those assays are substantially more sensitive.

High-Sensitivity Troponin vs Troponin

Dr Gulati: That's helpful. Why don't we go through how it differs from what we currently have with troponin I and troponin T in [defining an] abnormal finding and timing changes compared with our current biomarkers.

Dr Jaffe: The basic principles for the use of troponin remain the same, which is that you will see elevations in patients who do not have acute myocardial infarction [MI]—[they instead] have some other etiology for cardiac injury.

The numbers will be different because these assays are validated and developed differently. As a matter of fact, to avoid a problem of having too many zeros, we're advocating that people use whole numbers for these values. So they'll be reported in pg per mL or ng per L so that they will be 14 or 18 or 35. That means some numbers will be quite high, as high as 1000. It's better to do that than to use a lot of zeros and have someone in the middle of the night miss a zero and become confused and do something wrong clinically.

Dr Gulati: So it will be easier to recognize an abnormal value, but how about the timing? Right now, our patients come in, we do a 3-hour value and a 6-hour value. Is there a difference in the release kinetics, if you will, for the high sensitivity, or are we just getting it earlier in the release phase?

Dr Jaffe: A little bit, but not as much as you would think because biomarker release is related to blood flow, so if you have a completely occluded vessel, you're not going to have a lot of biomarker release.

That said, the increased sensitivity of the assays does cause—for a larger number of patients—an earlier signal. So you're going to push the diagnostic window toward shorter and shorter periods, but you're never going to eliminate, most likely, that occasional patient who still will need to be evaluated after 6 hours.

But we should get into that because, by and large, MIs are larger events from the troponin perspective, so we're not going to diagnose a huge number of additional MIs with high sensitivity because they're bigger, we're going to begin to identify a larger number of other reasons for cardiac injury that we'll have to sort out.

Sorting Acute MI

Dr Gulati: We'll come to that. I think that's a really important point. In terms of acute coronary syndromes, you mentioned that we're not going to be increasing the share of the identification of these larger MIs. That makes a lot of sense. But the small ones, the ones we are currently uncertain of in the emergency room, do you see us identifying a lot more genuine acute coronary syndromes in the emergency room?

Dr Jaffe: Well, what's going to happen is that unstable angina, assuming the timing is right to look for a changing pattern of values—which is really key when you have high-sensitivity assays and particularly when we're detecting these other sources for cardiac injury—will go away, and you'll have [non-ST-elevation MI] non-STEMI.

And the other good thing about it is that some rule-out protocols can even be done on the first sample because they're sufficiently sensitive. Since most of the comorbidities that lead to atherosclerosis cause increases, a very low value can effectively rule out patients.

So what's going to happen is that we'll see a signal earlier, and we'll get rid of unstable angina. The rule-out will be much more solid. The consequence will be fewer patients with acute coronary syndromes in aggregate who require admission to the hospital. The exchange for that is going to be more patients with heart failure who have elevations, but those patients are at risk; more patients with sepsis and acute respiratory failure; and a variety of other noncardiac issues that we're also going to need to sort.

Dr Gulati: That's the concern, I guess. The idea of the rule-out is very appealing, but I suspect, don't you, that there will be a much larger portion of patients who are the non–acute coronary syndrome elevated-troponin variety who will have positive identification. The question then is, what do we do with these patients? We don't know what to do with these patients, already.

Dr Jaffe: Well, there are two bins for that. One bin is the group of patients who have known cardiovascular disease, and they'll help us because that will define risk. A heart-failure patient with elevated troponins is at much higher risk than one with lower troponins. A patient with aortic stenosis or valvular heart disease is at much greater risk; the person who is having malignant arrhythmias, so that there is an appropriate use for this in the cardiovascular patient. There will be patients who have primary noncardiovascular disease, sepsis, acute respiratory failure, [gastrointestinal] GI bleeding.

Some of those patients could have an exacerbation of underlying coronary disease, but the vast majority do not.

What needs to happen and has happened very effectively in some European hospitals is to train people properly. Those patients should go to noncardiovascular services where they are seen by a cardiologist to make sure they are not one of the few patients who really have an acute coronary syndrome, and then they get their primary disease taken care of.

If we don't do that due diligence and readjust our systems, however, it would be easy to have them all admitted to cardiology because they have something wrong with their heart, and that would be bad both for cardiologists and also for the patients, because we probably don't take care of strokes, sepsis, or acute respiratory failure nearly as well as our colleagues who do that every day.

Uptake in High-Sensitivity Troponin Assays

Dr Gulati: So you mentioned about the European experience. Just to clarify, this is not yet in widespread use in the US?

Dr Jaffe: It has not been approved by the [US Food and Drug Administration] FDA. The Roche putative "high-sensitivity" assay and the Abbott assay are available throughout the rest of the world. The United States lags behind, unfortunately, in the ability to use these new tools.

Dr Gulati: So assuming that approval is forthcoming at some stage, do you expect the uptake to be wide and rapid, or do you think it's going to be a more graded progression to use here?

Dr Jaffe: It likely will mimic what happened in Europe, which is companies are unlikely to be supplying the rest of the world with [the high-sensitivity assays] and keep [selling the conventional] assay at a relatively modest volume. So the high-sensitivity assays will replace all of the non–high-sensitivity assays whether we like it or not, so I think the uptake will be fairly rapid, and we will need to adjust.

Dr Gulati: And the extra cost for the high-sensitivity assay compared with what we currently have?

Dr Jaffe: No difference.

Dr Gulati: No difference in cost.

Dr Jaffe: They are both relatively inexpensive [enzyme-linked immunosorbent assay] ELISA radioimmunoassays.

Dr Gulati: Just to clarify a point from earlier about serial high-sensitivity troponins, currently we look at the delta with our troponins. Will that be the plan for the high-sensitivity assay?

Dr Jaffe: That's going to be terribly critical, because the individuals who don't have acute coronary syndromes will fall into two bins. One bin of patients will have chronic cardiovascular comorbidities who could have elevations but without a rising or falling pattern. Those patients will need to be triaged based on their problem but not necessarily admitted because they don't have an acute cardiovascular issue.

There will, on the other hand, still be patients who will have a rising or falling pattern, for example, patients with sepsis; GI bleeding; or atrial fibrillation with a rapid ventricular response. Those people still will have a rising or falling pattern, but they are not quite the acute coronary syndrome patient.

High-Sensitivity Troponin and Chronic Diseases

Dr Gulati: We talked about acute cardiac and non–cardiac-associated disease. What about patients with chronic disease and chronic elevations?

Dr Jaffe: That's where high sensitivity is really going to be tremendously helpful. For example, there are already good data to suggest that patients who have left ventricular hypertrophy and have an elevated high-sensitivity troponin are at increased risk. We now need to take the second step and ask, "What do we do therapeutically?"

We now know that patients who have somewhat higher [values but] within the normal range are at increased risk for development of heart failure. So, one can begin to sort people who have comorbidities like obesity, diabetes, hypertension and begin to pick out those people who are at particular risk. Those algorithms are quite robust even now.

The next step that we have to take is to define how we treat those patients. In addition, in patients with stable disease, those with higher troponins do worse. So there's a huge amount of additional risk-stratification information that will help us in the management of patients. We just need to take those steps and figure out exactly what we do with that information.

Dr Gulati: Excellent. Thank you, Dr Jaffe, for these really important insights into a topic that we'll all be faced with in the near future, and thank you for joining us on on Medscape.


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