Hello, welcome to the Troponin Assays, the 411, a 30-minute highlight of the essential information on troponin assays. We've included this session in this year's Quality Summit because high sensitivity assays are coming to your emergency department, if they haven't already. We predict that by next year's Quality Summit, you will all be experts, and this session is designed to get you started on that transition to the newer assays. But before we begin, I must give a quick shout-out and special thanks to the meeting organizers Maria Ortiz, Maddy Tapp, and Connie Anderson for inviting us to speak. I, Christina Blankenship, have no disclosures related to this presentation. We have two learning objectives. I will start with a review of the basics, and then hand it over to Dr. Mike Kontos for a deep dive into a discussion of the high sensitivity troponin assays. So let's get started. To meet our first objective, we will discuss why it is that we can rely on troponins to support the diagnosis of patients with possible myocardial infarctions. We'll review the significance of important terminology, specifically upper reference limits. And finally, we'll review the implications that these newer high sensitivity troponin assays have on coding within NCDR. The basics of why we rely on troponin values for diagnostics requires a review of muscle anatomy and a touch of cell biology. So technically, we have three different types of muscles, smooth, skeletal, and cardiac. But this is the only time we'll mention smooth muscle, it's not relevant for the rest of this discussion. The troponin that we will cover is specific to the heart muscle and the skeletal muscles. In fact, that's part of the issue. Troponin is found in both cardiac and skeletal muscles. The cardiac and skeletal muscles are comprised of multiple muscle fibers, as shown in this diagram. Each muscle fiber is then comprised of sarcomeres. Within each sarcomere, we have multiple actin filaments, myosin filaments, and that troponin protein complex. This complex then has three unique parts. They're labeled troponin C, troponin I, and troponin T, based simply on their role in muscle contraction. Troponin C connects to the calcium, troponin T binds to tropomyosin, and troponin I inhibits specific movement during the phase of muscle relaxation. Troponin C is not used by the assays, so we can forget about that for this session. Now cardiac troponin T and cardiac troponin I are detected and used in the assays because they are specific to cardiac muscle. The results of these assays then indicate if there's been damage to the heart muscle. Also, almost all of our assays measured the subunit troponin I, and you'll see that abbreviated in the naming convention by TNI. Some assays in the registry are using protein subunit troponin T, and those are labeled TNT in their names. The assays can measure how much of the heart-specific troponins I or T are in the blood. That covers what troponin is, a building block of the skeletal and the cardiac muscle, but this leads us to the next set of questions. Why do the assays use troponin levels in the blood, and why do we rely on these for diagnosing patients with heart attacks? Historically, several other biomarkers had been used to support the diagnosis. The image on this slide is 11 years old and outdated. Guidelines have moved past using creatine kinase, CK, and myoglobin as markers. The scientific evidence points us to troponins as the gold standard. These are the most specific to identify cardiac muscle damage. The cardiac troponin proteins specific to heart muscle are released into the bloodstream when damage occurs to the muscle cell. The damage to the heart muscle occurs during a myocardial infarction, a heart attack, or damage will also be identified by troponins in the blood when any degree of myocardial injury has occurred. So while an increased amount of troponins measured in the blood is, in fact, specific to heart muscle damage, the hard part is knowing if it's the result of an infarction or just an injury. How we treat these two conditions, of course, is completely different. Diagnosing a myocardial injury versus a myocardial infarction is supported by the troponin value itself. This is where the concept of the troponin assay's upper reference limit becomes significant because troponin is a natural part of the muscular system, and we know the human body is constantly regenerating itself. There will always be a very small level of troponin floating around the circulatory system from this regeneration process. Studies have found small levels of troponin detected in healthy individuals without any heart damage. Again, very small levels. We know the ranges of troponin that are considered normal. The upper reference limit, abbreviated URL, identifies the highest amount of troponin that should be considered normal. If the amount of troponin measured in the blood sample is above this highest level of normal, then the value is considered abnormal and supports the diagnosis of a myocardial injury or infarction. The upper reference limit is established at the 99th percentile for each troponin assay. Values above the 99th percentile are considered abnormal when the values below the 99th level are considered normal. NCDR participants see these percentiles on dashboards for each measure in every registry. Each executive summary measure displays performance data in percentiles, providing the 10th, 25th, 50th, 75th, and 90th percentile. We know that if a hospital is performing at the 90th percentile, then the performance of that given measure is in the top 10% of all hospitals. That concept is probably familiar to everyone. Along that same trend line, though, to the right of the 90th percentile, we would reach the 99th percentile, where the top 1% of hospitals would be performing. So say the metric displayed here is the level of troponin found in a blood sample, then any sample at or above the 99th percentile would be higher than all but 1% of the samples. In this image, we see that the value at the 90th percentile mark is 100, and the values are increasing as you move to the right. It is reasonable to think that the value for the 99th percentile might be up to 103. So if a troponin level was 110, then it would, in fact, be greater than the 99th percentile. Because the upper reference limit for troponin assays is that 99th percentile, then that value of 110 is considered abnormal. This illustration provides actual troponin values in nanograms per liter, but displays the same concept as that earlier slide. Any troponin value less than the 99th percentile is considered too small to represent an MI. But if a value is above that 99th percentile, then the amount of troponin circulating is considered abnormal and significant enough to suggest that there has been cardiac damage, either injury or infarction. One last quote related to the upper reference limit, straight from the fourth universal definition of MI from 2018. The 99th percentile URL is designated as the decision level for the presence of myocardial injury and must be determined for each specific assay. The information can now be put into immediate use with the decision flow diagram also from the fourth universal definition of MI. The first step looks to see if the cardiac troponin is elevated or above that 99th percentile. Further steps that we haven't discussed are was there a rise and fall in the troponin value. And since there can be no trend line with just one value, more than one troponin test is required, three are required in order to see the direction of the trend line, whether it's up or down. The decision making is then in the hands of the clinicians. This is a good time to point out that the diagnosis of injury or infarction is not made entirely by the troponin value. The assay serves to support the decision. There is also more clinical decision making involved. So every time we see a troponin elevated, it's not necessarily indicative of an infarction. We now shift gears from speaking in general terms about all troponins to focusing on the specifics of the assays themselves. Troponin assays can be clinical laboratory based and those take about 60 minutes to run or the assays can be done at the point of care and they take about 15 minutes to run. Within the CPMI registry, the chest pain in my registry, the vast majority of the hospital data that we have includes laboratory assays. The concepts surrounding the upper reference limit for the assays is the same for all assays. However, the specific troponin value for the 99th upper reference limit is different for just about every assay. And Dr. Kontos will mention this also with his conversation of a high sensitivity assays. You really should know your hospital's assays upper reference limit. Your cardiologist absolutely should know it. The table displayed here is from the IFCC, the International Federation of Clinical Chemistry, and they provide these lists annually of all the assays available and all the associated URLs. Other terms in addition to URL that you may hear are LOB, the level of blank, LOD, which is the level of detection. They're out of scope for this basic 411 talk, but quickly, they represent the values at the far left end of the curve, the lowest troponin values that can be detected. So for diagnosing an MI, we are focused on the upper ends of those values. Another term, the percent CV, is of value to us. It indicates the level of imprecision that is associated with an assay at the upper reference limit. You will also hear a term delta and its associated symbols, which is basically a triangle, and it represents the amount of change between two values. So when your hospital starts using high sensitivity troponins, you will see two new levels for that upper reference limit, in addition to the overall value that we have now. Clinical studies inform us that the cutoff for abnormal values is sex specific. These assays will have male URLs and female URLs. The 99th percentile for females will be lower than the 99th percentile for males. This is an important point. It suggests that if we are not careful, females with heart attacks can go undetected, or they may go undetected, and we know from the clinical literature that this happens once by the way is way too often for this to happen. If the male URL is being used as the hospital's standard cutoff, and a female patient has a level above the female URL, but unfortunately below the male URL level, then can you see how her lab assay will appear in the normal range for that hospital? If I can only get one point across in these few minutes, and that's my biggest message regardless of what the learning objectives are, but this is happening now, and it is a huge opportunity for improvement in outcomes for females, please think about considering this as your quality improvement initiative at your hospital, and come back next year and tell us how it went. The fact that the troponin assays will have different URLs based on sex is also why the NCDR CPMI troponin list and the auxiliary data sets for both Cath PCI and CPMI were updated earlier this year to include every single URL for males and females. The various units of measure associated with the troponin assays introduces another level of complexity, but it is straightforward. Patients need to be aware that there are different units associated with different assays. There's also a resource document linked to both the Cath PCI and the CPMI resource pages that walk you through all of this, and in that resource document, there's a link to a useful online conversion tool. NCDR captures the values in Cath PCI, Chest Pain MI, and the auxiliary data collection tool, and it's vital that participants code an accurate value and an accurate unit of measure. NCDR relies on the troponin values and the units of measure for various important evaluations of our patients. One example being determining whether a patient is high risk in the Cath PCI appropriate use criteria metrics. Also in Cath PCI, the troponin unit of measure is specific to nanograms per milliliter. In the Chest Pain MI registry and the auxiliary data sets, you can select one of three different units of measure. They are nanograms per milliliter, nanograms per liter, or micrograms per liter. Because hospitals employ different lab equipment and there are multiple unit of measure options like we just discussed, and the range for each of these is very different, it's way too easy to code an erroneous value or select an incorrect unit of measure. This calls for extreme accuracy when extracting the data, specifically when the value reported at your facility does not perfectly align with the NCDR product. If you are converting a troponin result, if it is necessary, and because manually computed results are prone to user error, please use the free web-based troponin calculator. There's a link here in the image. There's also a link within the resource document. Troponin assays can have a distinct upper reference limit for gender, as we've discussed, but also specimen type, which some organizations may be utilizing. Alternatively, organizations have opted to use the nonspecific overall URL. To accommodate all these scenarios for both the point of care and the central lab, the master lists include devices which are the same, but the device name, as you'll see, is slightly different to identify when there is an option for a sex difference in URL or a specimen type difference in the URL. For those of you brand new to the Chest Pain MI Registry, this image is of the executive summary level measure, early troponin measurement after an NSTEMI. The measure is generated from the 2017 performance measures for patients with ACS, and it highlights how the CPMI Registry benchmarks the process participating hospitals follow to measure troponin in our patient population. It's now my great honor to introduce Dr. Mike Kontos, who among his many roles and responsibilities is also the chair of our Chest Pain MI Registry Steering Committee. I will hand the microphone over to you to cover the second objective, the deep dive into high sensitivity assays.

troponin assays

upper reference limit

myocardial infarctions

high sensitivity troponin assays

heart muscle damage