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Utilizing right troponin assay to diagnose MI is important
In part two of this round table, the panel discusses different assays and what to look out for when interpreting test results.
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Cardiology Today convened this round table in November at the American Heart Association Scientific Sessions 2007 in Orlando. Chief Medical Editor Carl J. Pepine, MD, moderated the discussion. Part two of the round table is presented here. Part one appeared in our February issue of Cardiology Today and can be viewed online at www.CardiologyToday.com.
CARL J. PEPINE, MD: Let’s say that we have a patient who comes in with a story that is not particularly typical of an MI, but the physician caring for the patient ordered a cardiac biomarker that is elevated. The patient then gets triaged to conservative care because the electrocardiogram doesn’t show ST-segment elevation. The next day the patient gets a coronary angiogram that shows only minor irregularities.
The traditional way to handle that in most of the centers around the country would be that this is not a myocardial injury. Given that scenario, what do you recommend that we do to better define that particular problem for that patient?
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Carl J. Pepine, MD
Joseph Alpert, MD
Bernard R. Chaitman, MD
Allan S. Jaffe, MDALLAN S. JAFFE, MD: There are two or three things that we ought to consider. The first is to start with the pretest probability of disease. If this is a 50-year-old diabetic woman who comes in with atypical chest pain, you may have a very different response than if this is somebody who has no risk factors and has just had a long trip.
Before you send someone to the cath lab just because the biomarker is elevated, you need to consider the clinical presentation.
The second issue is that in most clinical trials, about 10% of patients with ACS are classified as having MI because they have good stories, some minor ECG changes, rising troponins and normal coronary arteries. The idea that fixed atherosclerosis is the only thing that can cause MI is probably not correct. But if somebody comes in and they look like they’re having a classic MI, the fact that their coronary arteries may be normal does not necessarily exclude the idea that they’ve had an ischemic problem related to CAD. If the angiogram is normal, we may want to attribute that still to CAD, but we may also want to consider myocarditis, a common mimicker in the acute setting, or a variety of other things we’ve included.
BERNARD R. CHAITMAN, MD: It should be noted that there are different assays for troponin and CKMB, some of which may not be as reliable closer to the upper limit of normal. What if you did have just a very small elevation in somebody with atypical symptoms and you thought it might be the assay because you had one value that was up and the rest of the values were down, and the document says you only need one elevated value above the 99th percentile?
Are you going to call that single elevation an MI or would you be worried that maybe there’s an assay issue?
JAFFE: The assay issues that usually cause problems by mimicking elevations are cross-reacting antibodies and so-called heterophilic antibodies, which are antibodies to the material from which the antibodies are made. When present, they usually give one constant elevation without change. Good labs can exclude that problem. We have so-called heterophile blocking tubes that we can use and we can do dilution studies.
That said, it is also possible that things like a poorly spun sample that has fibrin in it could give you a false-positive signal. If clinicians are concerned, they should interact with the laboratory.
CHAITMAN: This is a universal MI definition to be applied worldwide, and the laboratories that measure the biomarkers may be in small hospitals and big hospitals, university hospitals, etc., with different quality-control procedures.
JOSEPH ALPERT, MD: I agree but I have two footnotes. Footnote number one is that you don’t just go in, notice that the patient has an elevated troponin, stamp MI in the chart and tell the patient that they had a heart attack.
The other footnote is that patients can have more than one type of MI. For example, the patient arrives at the ER with a classic type I MI, then they go two days later to the cath lab and there’s some little misadventure. An atrial side branch gets occluded and they bump their troponin again. Well, they now have a type I plus a type IV MI, and you can see other kinds of combinations. We would like to be able to list that in the trials, that a certain number of patients had reinfarction or a second infarct related to whatever else went on.
PEPINE: What are your recommendations for the diagnosis of reinfarction? Is it still to stay away from the troponins and to stay with the CKMB?
JAFFE: No, it is to move to troponin. It’s now very clear that although troponin may be elevated and often is for many days post event, when one has chest pain and an appropriate clinical syndrome suggesting reinfarction, the troponin values rise promptly. Unfortunately, there isn’t a large amount of data about this area, in part because often we take those patients back to the cath lab and treat them so aggressively. What we’ve suggested is a 20% change as a criteria. Get two samples and look for a 20% change.
CHAITMAN: Also, of course, you might have ECG findings to accompany the enzymes.
JAFFE: Of course. Again, as Joe pointed out just before, it has to be with the appropriate clinical scenario. If the patient is septic, it may well be that it’s the sepsis and not the MI.
PEPINE: Unfortunately, the troponin tests have become so readily available that they are reached for by noncardiologists almost routinely for every scenario from nausea and vomiting to hypotension. What we are left with as consultants, at least in my institution, is trying to sort all of this out for the patient as well as the physician.
I recently saw a 70-year-old patient who had documented CAD and multiple PCIs, but was stable. She came in for a knee replacement surgery. She was anemic. Her hematocrit was 28, and the anesthesiologist felt that her CAD should be corrected and didn’t want to transfuse her. They gave her intravenous iron and erythropoietin. She had an anaphylactic-type reaction to the iron. She became profoundly hypotensive. In that period she developed a miniscule troponin rise. There was a 10% rise in two of her three samples.
They kept her in the hospital overnight, discharged her, and brought her back for her knee surgery two weeks later. Postoperatively, the surgeon saw the troponin. He ordered troponins and she had another rise. The critical care people who were caring for her in the postoperative orthopedic suite told her that she’d had an MI. Her first visit back to me was unscheduled and I said, ‘Why are you back?’ And she said, ‘I want to know, did I have a heart attack or not?’
What do you tell people?
JAFFE: There are several things that are important about this. The first thing is that this is probably what we would call a type II MI. This is someone with underlying CAD who probably had supply-demand imbalance, whether it was due to the anemia or the anaphylaxis.
PEPINE: Or the surgery.
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JAFFE: Or the surgery. The orthopedic surgery community is starting to look at patients older than the age of 70 who are coming in for hip replacements. We’re going to start seeing a lot more elevations just like this. If indeed the underlying substrate is ischemic heart disease, she probably did have a small type II MI, and that’s why making that distinction may turn out to be important not only for her but for others. Understand as well that if the clinical scenario was different and she was short of breath, maybe she had a pulmonary embolism.
Another important point is that if one starts looking, whether it’s at the surgery studies or as we’ve done in a paper that’s coming out in critical care medicine in the critically ill, these elevations not only presage adverse short-term results but also suggest there is a long-term adverse prognosis compared with people who don’t have elevations.
Rather than simply saying we’ve gotten them out of the hospital and they’re “out of sight and out of mind,” take this lady and watch her more closely than you would the average person who went through such a surgery without an elevated troponin.
CHAITMAN: There’s an interesting study that actually relates to your patient called the FOCUS trial, which is examining patients who have had hip fractures and known CVD or elevated risk factors at baseline. The researchers randomized patients to either no transfusion for symptoms only, or to routine transfusions to get the hemoglobin up above 10 grams. The primary endpoint is walking time and how fast the patients convalesce.
These patients are on average in their early 80s. As part of the trial, there is a biomarker study where our lab is actually classifying the cardiac events in these patients, looking at biomarker elevations and ECGs before and after surgery, and then before and after randomization. It will be interesting to see recognized and unrecognized rates of MI in this elderly patient cohort.
ALPERT: You take the history and you look at the electrocardiogram. At times, I have found that the resident might have missed a half a millimeter of ST depression that wasn’t on the baseline electrocardiogram in a patient that had some kind of funny chest pain.
JAFFE: When I had my bike accident and had eight broken ribs, they took my ECG and they said, ‘You’ve got 3 mm of ST elevation. You’ve got to go to the cath lab,’ and I said, ‘Give it to me.’
There I am with a sling looking at the ECG saying, ‘Bring that ECG tech back. Put these leads in the right place.’
ALPERT: How about giving you thrombolysis?
CHAITMAN: You might have had a cardiac contusion.
JAFFE: No, actually I had a very bad pulmonary contusion. My troponins were normal.
ALPERT: I agree. Carl, I would say to this woman, ‘You’ve had a very small heart injury. We know it’s probably related to the stress of the operation and so forth, and we’re going to measure your lipids and probably double your statin. I notice a few systolic BPs in the chart of 150 mmHg, so I’m increasing your ARB or your ACE inhibitor. You’re not on a beta blocker so we’re going to put you on a beta blocker.’
PEPINE: I can’t help but ask the old troponin question about the patient with renal disease who, for reasons that are not clear to any of us, somebody orders a troponin and the patient has a normal coronary angiogram, no story to suggest MI and, better yet, the troponin doesn’t rise or fall, it just stays there.
JAFFE: The data in renal failure have progressed substantially. An 85-patient pathologic study from Daly Ooi in Canada included about 25% of patients who have renal failure; researchers looked at elevated troponins and, in every instance, there was something going on in the myocardium.
PEPINE: It has prognostic importance.
JAFFE: There is clear prognostic importance to these elevations. It is also clear that for patients with renal disease that present with an ACS, elevations have augmented prognostic value because the renal failure subset is at highest risk. It has also now been shown that if you want to distinguish between those more chronic elevations and acute elevations, you look for rising values in patients with renal failure known to have chronic elevations when they present with ACS.
A couple of caveats: First, there are more elevations of troponin T than troponin I in this circumstance, although with some of the more sensitive I assays they are coming close. Second, troponin T has been approved for risk stratification of dialysis patients. I suggest that dialysis patients should have such a value that they can be used as a comparator when they come in to the ER with a problem that needs to be triaged.
ALPERT: A comparable situation applies. Patients with dilated cardiomyopathy or severely decreased LV function secondary to CAD may have persistant low-grade elevation of troponin, and they are also at increased risk for morbidity and mortality and may be candidates for more aggressive anticoagulant therapy.
JAFFE: We recently published a paper in Circulation suggesting that, to our surprise, in following chronic HF patients changes in troponin markedly increased the hazard ratio. It may well be that we’ve always thought about this as patients having sort of a gradual decrease in function and chronic troponin elevations as you lose myocytes. It may well be that it’s a step function instead and that there are these unique episodes.
We detected them in outpatients, but the patients who present with acute HF almost always have such elevations. It may well be that there’s an opportunity to intervene in some appropriate way.
There are lots of troponin assays that are out there, many of them are extremely good, but many of them are not so good.
ALPERT: These are mostly type I MIs.
JAFFE: Yes, mostly troponin I assays. If indeed one is using a sensitive assay, one identifies a large number of the patients who are at risk. If one is using an insensitive assay, and most of the point-of-care assays fall into this category with rare exception, one is not identifying nearly as many patients at risk.
If you use the good assays – each clinician needs to know what assay they use at their local hospital and hopefully find out that they use a good one – know what cutoff the lab uses. Sometimes in the lab, for certain tests, we will change the cutoff value because we think it serves the clinicians better. Make sure they are using the 99th percentile.
We’ve put in the document the internet address for the web site that is run by the International Federation for Clinical Chemistry that provides what the appropriate values for each assay are.
PEPINE: What is the take-home message for our readers about this document?
CHAITMAN: The document should be used widely by the community. In some countries, however, where they may not be able to get troponin assays on a regular basis, such as rural Africa, some of the older criteria like using the electrocardiogram and clinical acumen may be the way to go.
We didn’t really talk much about the electrocardiogram, but there are some changes in the document about the electrocardiogram that are important. ER physicians as well as cardiologists should familiarize themselves with these new ECG criteria.
JAFFE: I hope that we can codify now in a consistent way across sites so that everybody is on the same page. We now have criteria that everybody can use and, if we use them, they will not only serve our patients and ourselves well but they will allow us to look across trials.
It is going to take some work from all of us to understand both the data and how to use the assays. It is not something that we like to do because it means relearning, getting rid of some old habits and learning some new ones.
ALPERT: I hope this is just the first of a whole series of attempts to globalize definitions for HF, various arrhythmias and a whole variety of clinical syndromes because these diseases occur all over the world.
When a cardiologist in Tokyo says, ‘This is a myocardial infarct,’ the cardiologist in Tucson is going to say, ‘I understand that.’
Seven to 10 years from now, we’ll have more data and we’ll tweak around the edges of the MI definition again.