Welcome to AACC's Expert Access Live Online program

Question: Our staff cardiologists are now attempting to change post-PCI orders claiming that ACC guidelines require cardiac enzymes to monitor reinfarction. They claim that TnI is TOO SENSITIVE to follow post PCI patients. The requests are to re-institute pre and post CKMB testing. I feel like I am going backwards. What do you suggest? Thanks Deb Motika
Reading PA

Alan H.B. Wu, PhD, DABCC : I have heard this story before also and agree for both your and the interventionalists points. This is a step backward as CK-MB is less specific, on the other hand, troponin is too sensitive. The middle ground is to use a higher cutoff for troponin that reduces the sensitivity but maintains the specificity. Unfortunately, there are no guidance as to the best troponin cutoff, unlike CK-MB, where many have used some multiple of the upper reference limit (e.g., 5 fold).

Question: Question One: what, in your opinion, are the optimum times for serial monitoring of CTNI, e.g, 0, 3, 6, 12, 24hrs vs 0, 6, 12, 24, etc., and what % change do you consider significant vs. biological variability? We currently recommend 0, 3, 6, 12hrs monitoring and suggest that a 25% change, either up or down, is significant. Question Two: Have you dropped CKMB from your cardiac marker panel and, if so, what may be the indications for use of CKMB (e.g, re-infarction)? Thanks, Lee Mell Clinical Lab Director Integrated Regional Laboratories 5361 NW 33rd Ave Ft Lauderdale, FL 33309
Ft Lauderdale, FL

Alan H.B. Wu, PhD, DABCC : Leroy, nice to hear from you. I certainly favor the 0, 3, 6 h intervals, taking into advantage of the higher sensitivity of troponin over MB. The 0, 4, 8 is ok but I think 0, 6, 12 is too long in my opinion. A person can easily rule out from 0 to 6 h and he/she is not waiting in the ER to rule in. We don’t offer a serial change cutoff yet, this needs to be further developed for specific assays for large numbers. 25% may be too small as this is within the biologic variation, where the reference change value is more like 50%. Yet other have advocated limits around this (e.g., Fred Apple, and Allan Jaffe). We have dropped MB entirely from our panel. There is some value for reinfarction since troponin does not return to baseline as fast. Fred showed in a series of infarcts that the second troponin bump from a reinfarction was just as evident (Clin Chem 2005;51:460-3), one could also get this information from total CK which should not be dropped because of it’s value for skeletal muscle injury (e.g., rhabdomyolysis).

Question: What are your thoughts on the establishment of a critical value for troponin, given that it is a contextual value. I.e., unlike sodium or glucose, which may be acted upon solely on too high or too low values, troponin value is interpreted in the clinical context.
Portland, Oregon

Alan H.B. Wu, PhD, DABCC : Critical value reporting can be important if it is done correctly. Best to report a value from the ED and only the first value, not all positives, as this becomes an annoyance. Some software is needed that can encode an algorithm for intelligent critical value reporting. On the other hand, one could argue that if someone orders an important test like troponin, that it should always be followed up, i.e., the ED staff should not need to be alerted. They may get into a bad habit of never looking at a lab result unless it is critical, so I am not in favor of instituting this unless you cannot get around it. I agree that the result must be interpreted in the context of the clinical presentation. A positive result, while indicating cardiac injury, does not mean AMI and is not necessarily a medical emergency (i.e., it would be expected in a patient with heart failure, renal failure, etc).

Question: At our hospital we have numerous physicians who order serial troponins with the comment "until peaks". Do you understand why the physician is interested in this? Our problem is the order is placed with no end time and does not always get cancelled appropriately. We have made the suggestion to order q6 hours for 24 to 48 hours since most patients will peak in that amount of time, but the practice is not changing. Any suggestions?
Cedar Rapids, IA

Alan H.B. Wu, PhD, DABCC : This is an unusual request by your ED staff. Peak concentrations don’t really mean much in terms of management decisions or diagnostic accuracy, and they don’t correlate to infarct sizing. Besides, as you mentioned, it becomes a logistics nightmare of ordering when not necessary and canceling when it might be important for a reinfarction. I suggest contacting your head of cardiology and ED services to get some consensus of the need for this practice and try to discourage it from a perspective of “bad medical practice,” unless they can convince you that there is some actual value to this (for which I doubt).

Question: Let's start with the basics. What is the difference between the two assays?
Ironwood, MI

Alan H.B. Wu, PhD, DABCC : This is an incomplete question, please re-pose. Difference between troponin T and I?

Question: Should I use a value of 99 percentile for diagnosis?

Alan H.B. Wu, PhD, DABCC : The 99th percentile should be used as the upper limit of normal, above which is indicative of cardiac injury. In the context of clinical signs and symptoms of ischemia, which may include EKG changes, this is an AMI.

Question: Can you please offer a bit more explanation regarding slide 4 and the difference between the troponin released by injured or stressed skeletal muscle vs. that released by damaged cardiac muscle?
Tempe, AZ

Alan H.B. Wu, PhD, DABCC : Slide 4 shows that there are significant differences in the amino acid sequence between skeletal muscle and cardiac tissue, particularly at the N-terminus. This enables the use of immunoassays that are specific for the myocardial forms and do not cross react with skeletal muscle forms. This slide also shows that the gene for troponin involves splicing of regions together.

Question: We measured concentrations of troponin I (Vitros 3600, 64 patients) of patients on chronic dialysis. There were no significant differences between results pre- and post-dialysis, and the results ranged from normal (<0,012 pg/ml) to high (1,23 at the beginnig and 1,27 at the end of dialysis). The results for NT-proBNP were high too. Our question is, What is you general experience with high sensitivity troponin I for patients on chronic dialysis ( end stage renal disease).
Clinical Hospital Sveti Duh, Zagreb, Croatia

Alan H.B. Wu, PhD, DABCC : Troponin T and I are positive in a fraction of patients on dialysis. These individuals are at increased risk for cardiovascular disease mortality. Unfortunately, there are no specific therapeutic measures to reduce CV risk in these patients so the information cannot be directly acted upon. Therefore one can question the utility of such measurements in the absence of symptoms suggestive of acute ischemia. In the latter case, results above the patients baseline at some higher cutoff, together with a changing pattern, may be necessary. There may also be no utility for measuring NT-proBNP

Question: Regarding serial changes, is it the total delta from the lowest reading to the highest reading regardless of the number of specimens, or is it just the delta between sequential samples that should be considered for risk evaluation. For example time 0 = 7 pg/mL, time 2 hours = 9 pg/mL and time 6 hours = 12 pg/mL.
Skokie, IL

Alan H.B. Wu, PhD, DABCC : There is no convention right now on how to report delta change values. If this is something you are going to encode into your LIS, there are some options: 1). changes between consecutive points, and 2) change from baseline to each point. Much depends on how consistent the timing and the blood collections are. In the absence of guidelines as to what serial change cutpoint is needed, the best is to alert the ED as to the importance of serial change and have them interpret results in the clinical context of the patient. By the way, I am a graduate of Niles West (albeit decades ago).

Question: Do you support the idea of CKMB for evidence of re-infarction and is there any protocol for increase of Troponin following initial Cardiac MI to confirm re-infarction?
Dixon, IL

Alan H.B. Wu, PhD, DABCC : I agree that CKMB can be used for reinfarction, but it is an insufficient reason to keep this test for this application alone. Troponin can also be use for reinfarction (see Apple Clin Chem 2005;51:460-3), and total CK can be used in the same manner.

Question: How Trop. value relate once it's reach to critically high, then continue with 3hr and 6hrs pathway? How advisable to do both Tro and CKMB assay for clinical point of view?
Wayne, Michigan

Alan H.B. Wu, PhD, DABCC : I am not in favor of doing both CK-MB and troponins and have dropped MB from our panel. As for the additional time points, if it is clearly a typical rising pattern over 2 or more samples, additional testing may be unnecessary.

Question: Why is it important to quantitate anything less than 0.05?
Sebring, FL

Alan H.B. Wu, PhD, DABCC : For diagnosis, it probably isn''t, but for risk stratification there is increasing evidence that changing troponin values, even in the normal range, portend poor outcomes. This is discussed in my review in Am Heart J. 2008;155:208-14.

Question: How much precission is required for an ideal Trop I assay?
Dhaka, Bangladesh

Alan H.B. Wu, PhD, DABCC : Ideally, <10% CV at the 99th percentile. But others have questioned the need for this (see Clin Chem 2010;56:941-3).

Question: Is there any clinical significance in using plasma vs serum specimen type?
Washington, NC

Alan H.B. Wu, PhD, DABCC : Some troponin assays don''t work well with serum, and some don''t work with plasma, although most work with either. Consult the package insert for specific details. There is no clinical significance for using one or the other except that using plasma enables a shorter processing time, as you don''t have to wait for blood clotting prior to centrifugation.

Question: Which Troponin is better, T or I? How do cardiologists interpret POCT Trop I (first with ED admission) and subsequent serial testing with Trop T (in Lab)?
Rockford, Illinois

Alan H.B. Wu, PhD, DABCC : Both markers are reasonably equivalent but it depends on the generation of the assay in use. Regarding POCT, there is no standardization of results against the central lab so it is difficult to start with POCT and follow with central lab results. I strongly suggest that the POCT sample be re-tested and reported by the central lab in addition to the subsequent samples for "baseline purposes."

Question: Do you recommend TropT over TropI for MI?
Palo Alto, CA

Alan H.B. Wu, PhD, DABCC : Both are largely equivalent, so it depends on the immunoassay testing platform that you have. This is the usual deciding factor, not the assays themselves.

Question: 1. Will low positive hsTNI results increase False Positive admits to the cathlab? 2. Will grey zone positive hsTNI results have any effect in reducing DRG313s? 3. Would a 0,90min multiple marker serial testing reduce rule-out decision time better than a single marker single draw or single marker multiple draw protocol? 4. Would a 20% CV affect the clinical relevance of a troponin assay result? 5. Will a POC solution reduce overall hospital costs by reducing time to decision and improving resource optimization? 6. What cut-off should be used: WHO vs 99th%? Thank you.
Mobile, Alabama

Alan H.B. Wu, PhD, DABCC : 1. Reducing the 99th percentile will lead to more positive troponin results and, if misinterpreted, more unnecessary caths. Therefore it is important that physicians understand that low level positives do not necessarily indicate an ischemic etiology. 2. Can you tell me what diseases are listed for DRG313 in order for me to respond? 3. I would caution about a 0 and 90 minute draw protocol. I believe others have said 3 h is minimally required for rule out. 4. Yes, 20% CV is relevant (see Clin Chem 2010;56:941-3), although a 10% CV is prefered. 5. PO can reduce overall hospital costs if the lab cannot deliver troponin results within 1 h, assuming that this is the "bottleneck" in the ED. 6. 99th percentile for POCT and central lab testing. The WHO should not be used today.

Question: How do you (or should you) risk stratify based on a troponin value (e.g., report ranges as negative, indicative of ischemia, suggestive of myocardial infarct, etc)? Most clinicians I know want cutpoints, not just values with a "normal reference range."
Atlanta, GA

Alan H.B. Wu, PhD, DABCC : This is a difficult question to answer. The lab itself cannot make a determination of risk stratification, AMI diagnosis or ischemia by the troponin test result alone. Clinicians who want this are unfairly passing the responsibility on to the lab. Clearly, reporting a normal range is the easiest approach, but some guidance is appropriate as to what a "low level" positive might mean (i.e., minor myocardial injury).

Question: If a patient presents to the ED, how frequently should you do cardiac enzymes/troponin? Should that frequency be different for 1. chest-pain ED patients being screened, and 2. for patients with MI after admission to the hospital?
Chattanooga, TN

Alan H.B. Wu, PhD, DABCC : I would suggest a serial testing strategy of 0, 3, 6, and 9hrs or 0, 4, and 8 hrs for screening patients with chest pain. For patients with AMI after admission, troponin testing might be useful for confirming the diagnosis or some indication of severity, but the testing frequency should be reduced.

Question: The combined use of troponin and CKMB was to address the 3-5 % of cardiovascular events that might have been missed by troponin alone. With ultrasensitive assays, is there still any utility with the combined use in regard to cardiovascular events, or are we pouring money down the drain?
Charleston, SC

Alan H.B. Wu, PhD, DABCC : Using the appropriate cutoff, i.e., the 99th percentile for troponin, there should not be any cases missed that are caught by MB. This is money in a sink after Draino use.

Question: There are so many so-called cardiac markers, all studied to be clinically useful. Can they be listed according to sensitivity, specificity, and clinical significance so that patients/clinicians can choose accordingly ?
Hong Kong

Alan H.B. Wu, PhD, DABCC : Probably not. Each study has different objectives, and therefore cannot be generalized against another. At best, we can compare the performance in terms of analytical specificity and analytical sensitivity head-to-head on the same sample set.

Question: Can you explain to me how we use the Apple scorecard?
Buenos Aires, Argentina

Alan H.B. Wu, PhD, DABCC : It's not really for routine clinical use, once you have selected an assay to use in your lab. But if you are looking to switch assays and want to know which is more sensitive, the Apple scorecard can help (i.e., the more of the normal range that can be detected by the assay, the better the sensitivity).

Question: Why use the hs Troponin assay? The 99th percentile is a biological/statistical cutoff that should not be affected by the sensitivity of the assay. I wonder if using the hs assay will significantly increase background noise (false positive)?
Boston, MA

Alan H.B. Wu, PhD, DABCC : I don't agree. Many of the troponin assays cannot measure low levels of troponin in healthy subjects, so the 99th percentile becomes the limit of detection. With high sensitivity, we can lower the limit of detection and the 99th percentile to catch more cases of minor myocardial injury. You are right in that along with sensitivity there must be precision, or else the background noise will increase causing some analytic false positives. Read also Clin Chem 2010;56:941-3 for more discussion on this.

Question: In your slide No. 11 (about the epitopes used in commercial cTnI assays), it illustrated the epitopes recognized by capture antibodies and detection antibodies. Some kits that were shown recognized more than one epitope. What I am asking is if one antibody can recognize two epitopes, or is it two antibodies that recognize two epitopes in these kits? For example, Abbott i-STAT; if it contains two capture Ab or one Capture Ab in kit
Toronto, Ontario

Alan H.B. Wu, PhD, DABCC : It is two antiobides that each recognize a different epitope. See slide 11 for the specific regions of the troponin peptide. From this slide, we can see that the iStat has 4 antibodies: 2 capture (regions 41-49 and 88-91) and 2 detection (regions 28-39 and 62-78).

Question: Do you see cardiac testing expanding more to the point of care? Most of the hospitals I work with say they are more comfortable utilizing their Main Lab analyzers, stating that they have greater accuracy & precision, and that the turnaround time is not a problem. Thank you for your answer!
Seattle, WA

Alan H.B. Wu, PhD, DABCC : If the central lab can produce a result within 1 h, then I agree that POCT is not necessary, since today''s POCT devices produce a result that is not as precise or sensitive as a result from the main lab. But if there are significant delays from the lab that cannot be reduced, then POCT becomes a viable option, especially for AMI diagnosis where time is of the essence. Once AMI is ruled out, ACS needs to be considered for risk stratification purposes, and the timing not so critical. The central lab will produce the best results for this purpose. However, there are next-generation POCT assays coming that will rival the central lab in analytic performance. Stay tuned.

Question: Have you evaluated TropT vs TropI using the Vitros 5600 and if so which would you recommend?
Palo Alto, CA

Alan H.B. Wu, PhD, DABCC : No, I haven''t evaluated these assays. I suggest that if you are currently a T user you should continue with this marker, and vice versa for the I as they will likely be equivalent.

Question: Concerning total CV < 10 %: Which protocol should be used to determine the CV for troponins? Andreas Reine.
Skien, Norway

Alan H.B. Wu, PhD, DABCC : This should be done day-to-day using 4-5 pooled samples with low levels of troponin ranging from just below the 99th percentile to perhaps 10-fold higher. The number of days is not fixed; an n=20 is ideal but may not be practical. A plot of CV (y-axis) vs. troponin concentration (x-axis) should be made. Where it intersects at 10% and 20% CV should be noted. The 10% CV argument is going by the wayside. See also Clin Chem 2010;56:941-3.

Question: We have been using the new-generation test from Roche Diagnostics for a few weeks. I have the feeling that we are now seeing slightly elevated TnT concentrations (up to approx. 40 ng/L) above the 99th percentile (> 14 ng/L) due to the intake of statins. Is there any evidence or study result confirming this observation? Gerhard Schumann
Medical School, Hannover, Germany

Alan H.B. Wu, PhD, DABCC : You are lucky to have the 5th generation assay that is not yet available to us in the US. I don''t think you will get increased TnT due to statin use as this relates to skeletal muscle injury and not myocardial injury (the very thing statins are trying to prevent) and the TnT assay does not have significant cross-reactivity towards muscle troponin.

Question: Can you clarify what is the best choice for POC cardiac testing in the ER? We are evaluating the Stratus CS because it is the same methodology as the lab's Vista analzyer.
Southaven, MS

Alan H.B. Wu, PhD, DABCC : The Stratus CS has the best analytical performance of any POCT device currently approved, although you could argue that it is more of a satellite assay and not a POC device. There will be next generation POCT assays that have higher sensitivity, but they are not yet FDA approved.

Question: What is the cutoff point for Architect? 0.3, per insert. Is that so?

Alan H.B. Wu, PhD, DABCC : Yes, but that will vary from instrument to instrument and lab to lab. It is best to determine the 99th percentile in your lab with normals (if possible).

Question: We have a pediatric patient with viral myocarditis who is displaying elevated cTnI on some assay platforms while negative on others. Is this expected?
New Jersey

Alan H.B. Wu, PhD, DABCC : Yes, there are different sensitivities for different cTnI assays. If you tell me the two platforms, I can comment further as to whether or not this is an expected finding.

Question: There is a great deal of support for utilizing a high sensitivity Troponin-I INSTEAD of CK-MB testing. Please describe the circumstances where you might support Troponin-I AND CK-MB testing.
Denton, Texas

Alan H.B. Wu, PhD, DABCC : Some have argued doing MB for infarct sizing, but I would suggest that a total CK is just as useful. Others have advocated monitoring for ischemic events after angioplasty or cardiac bypass surgery because cutpoints for troponin have not been established. We have discontinued MB entirely and have not gotten any negative feedback.

Question: Should there be any changes to the definition of healthy individuals when determining the 99th percentile with these new assays?

Alan H.B. Wu, PhD, DABCC : No, but it is not always easy to determine if someone is "heart healthy." Absence of events doesn''t rule out cardiac disease. Some have advocated testing for left ventricular function with BNP, and inflammation with hs-CRP, but this adds to your costs.

Question: What is the recommendation for testing, re: Troponin-T vs Troponin-I?
Sebring, FL

Alan H.B. Wu, PhD, DABCC : They are largely equivalent and the selection is generally based on the automated immunoassay platform that you have available for central lab testing.

Question: Could you please comment on the use of a Point-of-Care device like the iSTAT in the ED in comparison to the use of the high-sensitivity Troponin assays when attempting to rule out/in AMI.
Norfolk, Virginia

Alan H.B. Wu, PhD, DABCC : The iStat is not as sensitive as the central lab, and for risk stratification cases will be missed. For AMI rule in diagnosis, this is less of an issue as values raise rapidly above iStat cutoffs.

Question: Once ACS is confirmed with a POSITIVE cTnI value, how often do we need to order the test?
Markham, Ontario

Alan H.B. Wu, PhD, DABCC : Some would argue that you are finished, but there is definitely value in at least a second positive result to document a serial change.

Question: To clarify my earlier post, Is the biological variability of TnI the same as TnT? Can there be differences based on the sensitivity of the method?
Calgary, AB

Alan H.B. Wu, PhD, DABCC : In the two studies reported, they are not exactly the same. The variability for cTnT is slightly higher than for cTnI in the two published reports (Clin Chem 2009;50:52-5, and 2010;56;1086-90. This may be the result of sensitivity and precision of the assays involved, since CVa is part of the equations used in determining biologic variability.

Question: Regarding running Trop until endpoint... Does your facility stop once positive Trop is resulted, or how long once Positive by standards of infarct? Our cardiologist said he had references regarding death within 30 days post MI and wanted us to run until peak, even if Positive on 1st sample. Thank You
Dixon, IL

Alan H.B. Wu, PhD, DABCC : We don''t stop with the first positive. How many more are warranted can be debated. It would be good to know if the troponin values are continuing to go up or down.

Question: Since the 99% depends on popluation - will there become a standard way of reporting it?
Chicago, IL

Alan H.B. Wu, PhD, DABCC : That is something we are striving to do, but are struggling with. Ideally, we would like to create a single population of normal subjects and make it available to all manufacturers so that the 99th percentile is compared equally, but we have no funding for this program and it hasn''t started.

Question: iSTAT is being used in our ED for Troponin, and docs complain that the iSTAT reading is not comparable with lab. (iSTAT cutoff is 0.045ng/mL, Dade RXL analyzer is 0.6ng/mL). Sometimes the initial Troponin is done by iSTAT, then serial troponins are sent to lab and compared to iSTAT/ED result. Would you give us your opinion on this? Thanks.
Houston , TX

Alan H.B. Wu, PhD, DABCC : I agree with this protocol, so long as the initial i-Stat sample is repeated on to the RxL analyzer for "baselining purposes." Otherwise it will be difficult, if not impossible, to interpret the first result.

Question: What is the best marker for cardiac damage?

Alan H.B. Wu, PhD, DABCC : Without question it is cardiac troponin, T or I. Nothing else matters right now.

Question: Which troponin assay is more sensitive and specific, Trop I or Trop T?
Dhaka, Bangladesh

Alan H.B. Wu, PhD, DABCC : This question cannot be answered as there are multiple generations for troponin T and I. Sorry.

Question: At what level of sensitivity is a troponin assay considered high sensitive troponin?
San Francisco

Alan H.B. Wu, PhD, DABCC : Since there is no standardization, this is difficult to answer, but generally, a 99th percentile of <=0.04 ng/mL qualifies. There are next generation assay not yet available that will go down to 10 pg/mL for the 99th percentile.

Question: Many labs still use the ROC (AMI) cut-off. Is it not reccomended that the 99th percentile should be used as the cut-off?
San Francisco

Alan H.B. Wu, PhD, DABCC : Yes, labs should switch to the 99th percentile as the upper limit of normal. Diagnosis, however, requires positive troponin and clinical evidence of myocardial ischemia as well.

Question: A: What investigation algorithm would you propose with the hs-TnT assay for 1/diagnosis of ACS 2/prognosis or risk stratification of ACS? B: What time window would you recommend for serial hs-TnT testing in patients with symptoms of acute chest pain, presenting to the ED? (i.e. when should the first and second TnT test be done?) C: What delta change would you consider clinically significant with the hs-TnT assay? D: What hs-TnT cut-offs would you recommend for managing post-PCI and post-CABG patients?
Sydney, Australia

Alan H.B. Wu, PhD, DABCC : A. Right now, diagnosis and risk stratification of ACS is the same cutoff: the 99th percentile. Separate cutoffs have been proposed but have not been accepted by cardiology guidelines. B. I recommend testing at either 0, 3, 6, and 9 h or 0, 4 and 8. C. Cutoffs for delta change value have not been established. Some advocate 25%, based on biological variation, I advocate 50%. D. hs-TnT cutoffs for CABG have not been established. It will likely be some multiple of the upper reference range (99th percentile), but studies using this new assay have not yet been published.

Question: What markers need to be available at the ED bedside for patient management, and what markers should not be done at all?
Charleston, WV

Alan H.B. Wu, PhD, DABCC : I believe that troponin can be useful at bedside if the turnaround time for the central lab consistently exceeds 1 hour, as turnaround time for troponin is important for triaging and patient management decisions. BNP can also be done at bedside for management decisions in patients who present with shortness of breath and may have decompensated heart failure. The stat need for BNP/NT-proBNP is not as great as for troponin. Some have advocated D-dimer testing at the bedside for venous thrombosis rule out, but this is not widely done. None of the other cardiac biomarkers need to be measured at beside.

Question: What are the problems with Regulatory Compliance if "POC testing" is performed in the core lab?
Sebring, Florida

Alan H.B. Wu, PhD, DABCC : None whatsoever. However, in my opinion, the analytical performance of POCT is currently inferior to most automated immunoassays.

Question: We presently do baseline and 2 hour troponins in the ED. We do a total CK, troponin, and MMB at six and twelve hours if the ED patient is admitted to the hospital. What is considered the standard for frequency of cardic tests, and are MMB and total CK still considered necessary? --Gary Sellenrick
Sheridan, WY

Alan H.B. Wu, PhD, DABCC : There is no standard protocol. Your protocol is fine, although I would omit the CK-MB from 6 and 12 hours and just have troponin. Total CK is still useful for reinfarction and is very inexpensive.

Question: We run troponin assay using Elecys 2010 analyzer for more than 4 years. All the results have been less than 0.001, still the quality control is within range. In my opinion, I suggest that troponin is not a good indicator.
Addis Ababa, Ethiopia

Alan H.B. Wu, PhD, DABCC : Do you not have cardiac patients? If so, contact the Roche representative. Something is very wrong.

Question: The 99th percentile for the Access AccuTnI, Abbott AxSyM Troponin-I ADV and Advia Centaur TNI Ultra (XP/CP) is 0.04 ng/mL. The AMI cutoff in these is 0.5, 0.4 and 0.9 ng/mL, respectively. How could the AMI cutoffs be so different, yet the 99th percentile is the same?
South San Francisco, CA

Alan H.B. Wu, PhD, DABCC : These are likely the WHO cutoff concentrations, which is what the FDA wanted manufacturers to list originally. They are changing towards the 99th percentile, as recommended by cardiology practices.

Question: How should POCT troponin cut off be set (managed) in relationship to the high sensitivity troponin in the central lab. The ED doctor does not want the POCT/central lab troponin to be overly sensitive and clog up the ED observation unit. Should these patients with low levels of high sensitivity troponin be followed by their primary care doctors?
Boston, MA

Alan H.B. Wu, PhD, DABCC : The guidelines all say use the 99th percentile as the cutoff limit. The ED staff must be educated that this does not necessarily indicate AMI or ACS, and there must be clinical evidence of myocardial ischemia. Without this knowledge, I agree that it will be difficult to adopt lower cutoffs. Serial testing can be helpful to rule out AMI/ACS if there is no change in results.

Question: Do you have any guidance on using troponin testing in children, including in the first year of life? We sometimes see levels slightly above the 99th percentile of adults in the newborn period.
Vancouver, BC

Alan H.B. Wu, PhD, DABCC : I would not suggest using troponin in newborn unless there is a specific clinical purpose. Why are they asking for testing?

Question: If available POC tests are not as sensitive as the main lab tests, is there a place for these POC tests in our ER?
Naples, FL

Alan H.B. Wu, PhD, DABCC : They are effective for AMI rule in, as patients will release large amounts of troponin and decisions can be made eariler with a faster turnaround time result.

Question: What is the current status of standardization for troponin assays?
Atlanta, GA

Alan H.B. Wu, PhD, DABCC : There is a standard material available from the National Institute of Standards and Technology, but not all commercial vendors have adopted it. Even with universal adoption of the standard, there are differences in the antibodies used (see slide 11) so there is no standardization right now for cTnI. Only Roche has cTnT, so there is standardization across their platforms.

Question: Do we know the biological variability of TnI and TnT?
Calgary, AB

Alan H.B. Wu, PhD, DABCC : Yes, there are several papers now available in Clin Chem (e.g., 2009;50:52-8, and 2010;56:1086-90).

Question: Is it reccomended to use filters on all plasma specimens before testing Troponin?
San Francisco, CA

Alan H.B. Wu, PhD, DABCC : Are you referring to plasma filters? I would say no, just centrifuge with enough force and long enough.

Question: We've all gotten pretty good at detecting AMI utilizing varying POC cardiac marker protocols. What we need now is a way to detect the cardiac "problem" before it becomes AMI. What would be your criteria for sensitivity, specificity, etc. for a single marker--Troponin-I--to be utilized to accurately detect/diagnose ACS?
Denton, Texas

Alan H.B. Wu, PhD, DABCC : The 99th percentile for troponin is still the best strategy for detecting ACS as well as AMI. There is much research ongoing to find a biomarker that can detect ACS before full-blown AMI (e.g., myeloperoxidase, CD40 ligand, placental growth factor, pregnancy associated plasma protein A, ischemia modified albumin, free fatty acids, glycogen phosphorylase BB), but none have emerged as standard practice due to various deficiencies in clinical performance.

Question: On the slide, ''cutoff at the 10% imprecision limit," the arrow is pointing to 0.06 ug/L at 10% imprecision. There are also plots at 0.07 and 0.14. Are those specific or just indicating increasing precision. Our cutoff is set at 0.06 ug/L for a pair of Siemens Vistas Are there any papers or opinions on results between 0.06 ug/L and 0.10 ug/L in regard to patient outcomes?
Steubenville, OH

Alan H.B. Wu, PhD, DABCC : The data at 0.07 and 0.14, along with 0.04 and 0.02, are the actual data points used to contruct this plot. In general, results above the 99th percentile are indicative of increased cardiovascular risk. I am not sure if there is data specifically for the Vista. I suggest you contact the Siemens reps.

Question: In your opinion, which is the best performance to do troponin I in diagnosing patients with chest pain (sensitivity and specificity): Pathfast vs ECI by Ortho.Thank you.
Bogota, Colombia

Alan H.B. Wu, PhD, DABCC : I have no direct experience with Pathfast. The ECi is an excellent central laboratory-based assay. My understanding is that Pathfast is a POCT on whole blood. In general, POCT assays are not as sensitive as the central lab. I would suggest that it is likely not as good as the ECi.

Question: We are trying to establish parameters for our patients who come to the ER with acute coronary syndrome. The group that we are most concerned with are the non-STEMI patients. We have been using a cutoff value for TnI of 0.2 ng/dL in these patients using our old assay with good results. However the newer assays are more sensitive and we are trying to establish what the cutoff should be with the current TnI testing. We are using the Abbott assay and are leaning towards using a 0.1 ng/dL cutoff and doing serial troponins in patients between the 99th percentile and that value. What are your thoughts?

Alan H.B. Wu, PhD, DABCC : I definitely recommend lowering the cutoff and adopting serial testing. Values between the 99th percentile and 0.1 are associated with adverse outcomes, so this should be noted in addition to serial testing.

Question: In your response to Lee Mell, you recommended not dropping CKMB and CK in order to continue monitoring reinfarction and myocardial skeletal tissue damage. We have just started testing BNP, and the trade off for the cost of this test was to reduce the CK, CKMB, and magnesium tests, and just evaluate using BNP and Troponin-I. Do you think this is a feasable trade off, based on your opinion above? Dianne McCabe, Resouce Team Leader, Southlake Regional Health Centre
Newmarket, Ontario

Alan H.B. Wu, PhD, DABCC : Magnesium and CK testing are extremely inexpensive and will not save you much so I don''t agree with this strategy. Eliminating MB will save your institution money.

Question: Dear Dr. Wu, could you comment on the requirements for sensitivity of a cTnI test for diagnosis and treatment of patients at time of visit in an emergency room? Would “high-sensitivity” cTnI assay improve the care in such setting? In which setting(s) do you foresee the need for improvements in sensitivity (over existing commercially available cTnI assays). Thank you, Vincent Linder
Woburn, MA

Alan H.B. Wu, PhD, DABCC : Increased sensitivity for troponin will enable a slightly earlier diagnosis of AMI and triage of patients to the appropriate level of care. It will also generate a higher number of patients identified as high risk for future cardiac events. There are next generation troponin assays that have improved analytical sensitivity (to 1 pg/mL), but they are not yet available.

Question: Will grey-zone-positive hsTnI results have any effect in reducing DRG313s? This DRG is for non-cardiac chest pain. Admitting the patient perhaps unnecessarily when patient could be discharged quickly with a multi-marker serial (0,90 min) protocol at the POC setting (ED).
Mobile, Alabama

Alan H.B. Wu, PhD, DABCC : Yes, they likely will. But if someone has chest pain and an increased troponin, then they probably shouldn''t be in the "non-cardiac chest pain" DRG.

Question: Have any 4th generation TnI assays been cleared for use by the FDA?
Washington, DC

Alan H.B. Wu, PhD, DABCC : Only Roche lists their assay as “4th generation” for cTnT, and it is not FDA cleared yet. For cTnI, there are multiple generation assays, but they are not labeled as such. None of the highest generation of assays, as mentioned in Dr. Apple’s “scorecard,” are FDA cleared.

Question: Does an elevated troponin result mean that I've had a heart attack?
Ogden, UT

Alan H.B. Wu, PhD, DABCC : No, it simply means that you have had cardiac damage. Myocardial ischemia is the most common cause of an elevated troponin and produces the highest concentration. Other causes of minor increases include heart failure, renal failure, pulmonary emboli, valve disease and cardiotoxic drugs. Increases in troponin in these contexts are associated with poor outcomes.