How high-sensitivity Troponin T is reshaping ACS diagnosis and ED efficiency

Guest speakers:

Dr Diego Segura Rodriguez - Cardiologist, M.D, San Cecilio University Hospital, Granada (Spain)
Dr Pierre Sabouret - Cardiologist, M.D, Pitie Salpetriere APHP University Hospital, Paris (France)

Dr Giuseppe Galati - Cardiologist, M.D, M.M.SC, University of Milan, Milan (Italy)

What are some of the biggest challenges in making early and confident diagnostic decisions?

Dr Diego Segura Rodriguez: I think in acute coronary syndrome, we face many challenges. First, the diagnosis of ACS is critical because time is myocardium. So we have to do a quick approach to every single patient. Talking about diagnosis, troponin is crucial. And, as much as we can be accurate to the diagnosis, with high-sensitivity troponin, I think, is one of the assays that could be performed in less than ten minutes, but also, I may say that blood tests with high-sensitivity troponin may be extracted as soon as possible. So I think there are three critical points. We face some analytical interferences, especially from hemolysis, that may require some sample redraws. The second challenge that we used to face is biological variability in low troponin values, where imprecise definitions of healthy populations can inflate our 99th percentile thresholds. The third is turnaround times failing to meet the less than 60 minutes target due to analytical, broad analytical delays may challenge us to find the accurate diagnosis. 

Dr Pierre Sabouret: As highlighted by Diego Segura, in clinical practice, time is muscle. So the earlier the diagnosis, the better is the prognosis. So for us, it is crucial to have this tool in ICU in order to stratify the risk and to put the patients in the cath lab, because this is the best treatment in the short term.

The other aspect, very interesting for us cardiologists, is that troponin is also a very useful cardiovascular tool in the long term after acute coronary syndrome, because you can see the response of its biomarkers under treatment. If you have an intensive treatment for lipid-lowering treatment, blood pressure control, diabetes control, it is linked to a decrease of troponin and it is associated with a better prognosis. So for us cardiologists, it is not only the acute phase but also after the acute phase. So this tool is very crucial that remains underutilized by cardiologists, due to a lack of knowledge and sometimes lack of availability.

Dr Giuseppe Galati: Yes, I agree with both of them. I think they face the most reliable aspect about the ruling phase. Of course, you understand that ST-elevation myocardial infarction is not really a problem because it's self-explaining, self-showing. The problem is about non-ST-elevation myocardial infarction NSTEMI in which the management of the troponin, the performance of troponin entails problems related to the knowledge of emergency physicians, that is, you know, they are very, very few and not always very, very well trained in these settings.

And also about, you see, the organization of the emergency department, because as you understand, in Italy, but I think globally, they are largely understaffed and overcrowded. The most important is to have a reliable test because, in our clinical practice, we have several confounders, in Europe, as well as Japan, United States. We are having a huge problem. No problem; it’s the demography. We have a lot of aging. The mean age in Italy is 46 years. And we have Italy, Spain, and also Japan, they are the three countries where we do see the highest percentage of elderly people on the globe. And these people, they have several comorbidities that may be confounders. So to have a reliable troponin is a game changer.

Dr Sabouret: As you know, Giuseppe or Diego, there are some differences according to centers and expertise. For example, even in our center in Sorbonne University, we have the emergency department where sometimes the troponin interpretation is misused or suboptimal. And we have also a chest pain unit in which a troponin is very useful and, due to the high specificity, is very useful to stratify the risk by experts.

Dr Galati: Yes. This is the issue. The main issue.

Dr Segura: I think there are many variabilities, not only between countries, but also between centers even in the same country. Here in Spain, we have, as you mentioned, some hospitals with chest pain units within the emergency department (ED). But I think it's not the rule. And sadly, because I think it depends on the resources from the hospitals. The overcrowding that Giuseppe mentioned, I think is one of the biggest limitations, the short time per patient because they are too demanding, of course, because there are many patients coming and coming. As Giuseppe mentioned, I think education and giving a good education to our colleagues from the emergency department in terms of interpretation of the high values depending on the comorbidities that may confound, or may limit the exact analysis of, for example, Type 1 myocardial infarction versus Type 2 or other causes of high-sensitivity troponin elevation. I think it could be mandatory for all of us to provide this education as well as having some kind of high-sensitivity test to rule out this type of acute coronary syndrome (ACS). This  could be the first step to try to rule out these poor prognosis entities, as is the acute coronary syndrome; without ST-elevation we discussed. But the first step is to not make any discharge if there is any suspicion of acute coronary syndrome. 

Dr Sabouret: These words said by Giuseppe, for STEMI, that's not the issue to have the troponin because for STEMI, the diagnosis is made by the rest ECG and chest pain. So the clinical presentation is enough to have a diagnosis and to put the patient in the cath lab.

The main issue, as you said, is with NSTEMI, with over-diagnosis. But also the issue for attendees is not because you have a normal high-sensitivity troponin that you don't have coronary artery disease. So we have some patients we will rule-out for acute coronary syndrome. But that doesn't mean that they don't have chronic coronary disease. So it's very crucial for attendees because some patients will be ruled out. But you say, okay, it's not an acute coronary syndrome, but they need to be managed for their coronary artery disease.

Dr Galati: Yes. And again, both of them, they treated two other main points that are the heterogeneity of settings, and also, you see, the major problem is the lab. The first one, you understand, is not only the heterogeneity of the setting. For example, in Germany, there are emergency departments that are managed only by cardiologists, for example, in Heidelberg. But, you understand we have heterogeneity of tests: Troponin T, I, high-sensitivity, and the major issue especially, for example, also in Italy, but I think in other countries in some peripheral centers, there is still Point-of-Care troponin, PoC troponin that of course is not high-sensitivity. And this PoC troponin, of course, is assessing a fast management but is not reliable because... So we did for example, a study and we saw that a PoC troponin, negative corresponded to high-sensitivity troponin positive, and the opposite. So it brings you to false positives and false negatives. So to have automated assays is important, and in the future, I think also to develop in peripheral centers, you see, on the mountain, and very close to the sea, PoC troponin - this is very important.

And another element, for example, is that overcrowding and understaffing brings you to inaccurate clinical history and examination. And of course, in this case, troponin is the major “helper” of the emergency physician because otherwise they always call... you see, systematically they call for the cardiologist for an imaging test. So you see there is an abuse of this, especially for legal and medical issues. And we are sliding into the second major problem: the rule-out. To have the high-sensitivity troponin, for example like last generation very reliable, is very important for the lab because, the vast majority of chest pain that they access the hospital into the emergency department, they have a percentage of 80 and 90% that they don't have acute coronary syndrome or acute cardiac condition. So only 10 to 15% have an acute coronary syndrome or a pulmonary embolism, aortic dissection, whatever. So it's very important to have a test with reliability, to exclude patients that are in normal ranges. And to validate this in the general healthy population and to stay safe also for the emergency physician that does not always have to involve all the facilities of the hospital, the cardiologist consultation, the echocardiography, the CT scan. Of course if you have one, two troponin in the 0/1-hour algorithm or 0/2-hour, okay, it's enough for ruling out. And of course in the clinical scenarios where the chest pain probability is low, there are no other, hemodynamic instability whatsoever, so these two points are also very important,

Dr Segura: I absolutely agree. As we were talking, I remembered that some patients in the population are more educated, as artificial intelligence is telling them the symptoms that they are feeling or kind of that. There are many patients that I see more frequently that are coming to the hospital as soon as they can. I'm talking about early presenters. So, patients that come to the hospital as they feel the first tiny chest pain. So sometimes when they are coming too early with the classic series of high-sensitivity troponin analysis, this kind of test may under-diagnose... if we apply the 0/1 hour algorithm, they may rule out the acute coronary syndrome. But hopefully thanks to the new assays as the Gen 6 algorithms and assays, they may be ruled-in into the acute coronary syndrome diagnosis, compared with the previous one, with the previous assay. So I think we are in, hopefully, an era of high-sensitivity troponin assays that don't return any people with current acute coronary syndrome events in the early, earliest stage of the beginning of the process.

Dr Sabouret: Yeah. To cut a long story short, if you need to have best management of acute coronary syndrome, you need to have high-sensitivity troponin for non-ST elevation. So it's always a combination of cardiovascular history, of cardiovascular risk of patients coming into the ICU or emergency department. And obviously, I don't think that cost is a major issue. All departments now should have high-sensitivity troponin, because we have several publications that we cannot summarize now, but several publications which report the same findings, that high-sensitivity troponin is the best tool for the early diagnosis and accurate diagnosis of acute coronary syndrome.

Dr Galati: Yes. And another final challenge is that there are patients with multiple chest pains over the last day or days. So in this case also, this is not very well treated in the guidelines, the most important chest pain is not the first one, but the last. For example, on the same day you have a man or a woman with the first chest pain at 3 a.m., another chest pain at 6 a.m., and then another chest pain at 10 a.m. and they are coming to the emergency department at 11 a.m. Of course, you know, because we also had a problem with this in the clinical arena, you don't have to count the first chest pain, but the last. And because, for example, you can have unstable angina preceding myocardial infarction, and so to have a high-sensitivity troponin is also helpful in this case to do a 0/1h, 0/2h determination to be pretty sure that this is not myocardial infarction.

Dr Segura: And talking about this kind of patient that we usually face, as… diabetes, even women may feel different, not only atypical, but I mean, different symptoms of acute myocardial infarction. I think maybe in med school, we learn it as the typical chest pain, the angina is the only way to have a myocardial infarction, and this is not true. We usually face atypical symptoms that... this is not atypical, but different... like shortness of breath, dizziness, or other symptoms that may confound the clinical picture of the patient.

Dr Sabouret: As you mentioned, Diego, you have less and less typical chest pain. We don't know why. It's not only the women. I am against this idea that women always have atypical chest pain. That's not the case. But in general, not only women, but also diabetes T2, as you mentioned, elderly patients, patients with chronic inflammatory disease, they do not always have a typical clinical setting of chest pain, but in general, not only women because it's always said that women have atypical chest pains, but it's not only the case. But globally, we have less and less typical clinical settings, so high-sensitivity troponin is very crucial in this setting. 

Dr Galati: Yes. And also, let's not forget some patients with peripheral neuropathy. And, as Pierre knows very well, it's not rare that in the chronic setting we see diabetic patients that had myocardial infarction completely asymptomatic. So it's very common to find daily routine activity.

From a scientific and analytical standpoint, which elements of the new Gen 6 assay stood out and how could they help address these challenges?

Dr Galati: So in my view, the sixth generation, it's a game changer because we have at least two important studies, PERFORM-TSIX and REF-TSIX that are very important, especially the REF-TSIX, because it is a validation of the high-sensitivity troponin of the sixth generation with a really true healthy population. So, they enrolled more than 4000 patients across the globe represented in a lot of countries: Europe, United States, Asia, China, Japan, and they excluded several conditions also that they can be subclinical heart disease, so they exclude diabetes patients, those that take medication for lipids, for hypertension, smoking people, diabetes people, pregnancy, people with trauma, chest trauma, or weak cardiac symptoms, they can be referring to heart disease. 

And impressively they also performed an NT-proBNP on all the patients and they excluded all patients with value above 125. So they really enroll the truly healthy population as Diego told before to avoid the inflated value of troponin and with the mean also...a good mean age because 48 years old is very representative of the current demography. And they validated this with a method that is very good because it is very resistant, ten times to hemolysis, so of course, you understand that in the emergency department, when you do the blood sample, it's a very chaotic situation. So of course, the blood sample... they are not always perfect, you understand? To have a sample that is resistant to hemolysis and also if you do, for example, lithium heparin or serum, you see the difference. The sample is always the same result. And they found that with this, it was very good. They found the threshold, a unique threshold, universal, but also two sex-specific thresholds, 27 for the universal, 18 for the women and 32 for the male. You know that this is not still supported by the guideline that they endorse only one threshold. But the previous... the older universal definition of myocardial infarction from 2003 gives it support. And I think personally that this is better because, for example, for hemoglobin we have different values for the male and female. We have a lot of debate, but we are going for different values of the left ventricular ejection fraction for female and male. So I think it's good to have a sex-specific threshold.

And also they were able to see and they validated this accordingly to the International Federation of Clinical Chemistry. That they wanted more than 50% of detection involved. You see the low limit of the detection of 1.5 they achieved in this trial 90%. So very accurate, very reliable. So if this is negative, it is negative. If it is positive, it is positive. This is very simple for the people. And also they exclude obesity. Another important thing is the other trial that they just presented... I think 15 days ago in this European Congress. It’s PERFORM-TSIX, in which they achieved the primary endpoint that was to show the clinical efficacy to detect acute coronary syndrome, with the center validation and also with 0/3 hours and also they validated the other two protocols 0/1h and 0/2h. So these high-sensitivity troponin, the most important thing is that it is very accurate, very reliable. And you see, the pre-analytical and post-analytical fluctuation. So this is one of the major challenges that you want when you use the troponin in the emergency room. And I think also my colleagues, they think the same.

Dr Segura: I think there is little to add to the great explanation from our colleague, Giuseppe, I think, you sum up very well the good points of Gen 6. I think the validation of a huge population, healthy population with no comorbidities, but also, as you mentioned in the recently presented study, in people with suspicion of acute coronary syndrome. So we have a very well validated Gen 6 high-sensitivity troponin. And as we were discussing the huge variability of the emergency department, analytics people, kind of professionals working out there. I think giving these more precise values with less interference for hemolysis... You mentioned more that ten fold more resistant to hemolysis. We know how the emergency department works, that everybody is in a race with their blood sample running to the laboratory test. So may influence to hemolysis, so this kind of resistance for hemolysis, I think its impact on the clinical results, as for example, redraws, more reliable results, faster diagnostic decisions. As we mentioned, time is myocardium, so we have to rule-out and rule-in as quickly as we can.

Dr Sabouret: So also to mention the high specificity of this high-sensitivity troponin. It's also cost-effective, because it's crucial also to be cost-effective. And when you see how you can do an accurate diagnosis, also, an early rule-out or an early transfer to the cath lab for PCI is really cost-effective. But it's always another aspect very important to hospitals, but we need to use this tool more,  because if it's also cost-effective, we need a new global approach. 

Dr Segura: Yes, time consumption of the medicine department, resources, the chair that the patient has to occupy in the emergency department, maybe be useful to another patient. These patients, sending as soon as possible to the cath lab. Maybe even with this kind of urgency, Gen 6 assay, maybe use the “one and done” test. In other words, just one determination with the rule with six nanograms per liter cutoff at t=zero, may allow a safe release of almost 30% of patients, according to studies with 99% sensitivity, with zero, and this is crucial, with zero MACE, in other words, major adverse cardiovascular events, at 30 days. So I think it is a game changer in clinical practice.

Dr Sabouret: Concerning the guidelines, as Giuseppe Galati highlights, there is some progress to do. But as you mentioned, you have an amount of new proof, of new data about high-sensitivity troponin that probably we will have an update in this setting. And the most important for the guidelines, as Giuseppe and Diego knows, is that the guidelines should protect patients from non-experts, but experts should protect patients from guidelines. 

Dr Galati: Yes, because also the clinical scenario is more complex than the guidelines. And as Diego told it's important to underline that PERFORM-TSIX has a six month follow up. So it was correlated with the major adverse event, the MACE at six months, that is also important to remember. And also we have to think that this troponin will allow us to give also proper treatment and to avoid the use of resources because, as you understand, there are different hospital settings, for example, like in Italy, when more or less the cardiac consultation is automatic, echocardiography is automatic. And of course, this is also suboptimal because always we have few cardiologists in the hospital, and you take a cardiologist that probably is occupied more by the intensive care unit, where they already diagnose a patient in a severe situation. And you have to go to the emergency department, for example, to discharge a patient with 2 or 3 normal troponin, for example.

So to have a reliable troponin, this can help you also to avoid the overuse, of course, the facility of the hospital. And also, we accept cases over the patient, say more than one day because there were uncertainties... I think we will also treat very soon or soon the challenges in the clinical arena. But of course, for example, there is useless asking for the CT. And the major issue also beyond the rule out is the Observe phase, because of course there are routine rule-out. But the most difficult patient they are, that in the gray zone, when you need to observe in that case, to have a reliable troponin can be a game changer.

What are your perspectives on the study results, particularly the IFCC criteria or NIST reference?

Dr Segura: Yes. I think the IFCC criteria is quite strict. And I think the REF-TSIX methodology applied to these kind of strict criteria for the first time in healthy populations, recruiting almost 80,000 participants, of which more than 4000 were available, and this methodology excluded as mentioned by Giuseppe, patients with cardiovascular disease, chronic kidney disease, diabetes, NT-proBNP more than a slight value like 125 nanograms per liter and treated hypertension. And this methodology prevents threshold inflation that could delay the diagnosis. We were talking about gray areas. Here in almost 90% of healthy subjects, so detectable values, far exceeding the IFCC criteria of more than 50%. So these kinds of strict criteria were applied for the REF-TSIX methodology, and with great correlation.

So, aligned with the guideline TSIX, I think aligned perfectly with the universal definition of myocardial infarction, published in 2019, by validating even that, we were talking about the challenge, which is sex-specific thresholds as recommended for the guidelines. And talking about the ESC guidelines, it validated the 0/1-hour and 0/2-hour algorithms with 99%, 8.7%, almost 100%, of negative predictive value for safe exclusion. Except the IFCC criteria, with almost 90% of detectable values and with a great threshold for 99% percentage cutoff for cardiovascular events in the NIST, to ensure future regulatory and compliance and global standardization of troponin measurement.

So in summary, the IFCC strict criteria guided, and REF-TSIX applied to these kinds of strict criteria, with our great negative predictive value, almost 100%, according to our guidelines, or ESC guidelines, and according to the universal definition of myocardial infarction. 

Do you have any perspectives on how this evidence might shape future guidelines or clinical decision-making? 

Dr Galati: I can say that I think in the future, it's very likely that we have to adopt a sex-specific threshold. This is very, very important. So I think in the future, the acute coronary syndrome will adopt these and not a universal threshold. 

Of course, this is a very robust platform. I think the next guidelines will suggest a plethora of troponin. I think we have to start to restrict the field to the most performative ones, where troponin will give more performance, to give an early and safer diagnosis and reliable. Honestly, I can just anticipate something that I was going to say. I think that probably in the future guidelines, we are starting to talk about some AI algorithm for the interpretation of troponin. For example, this year has been validated this chest pain triage that is an AI interpretation of troponin. And this is very important because it is able to correct a lot of critical problems and mistakes that are done in the different emergency departments. For example, when you start to take the blood sample,...  we have to tell the tool, it’s like in the four pillars for HFrEF. (...) the patient, the practice,...  the use is very suboptimal. So, in this way, the last guideline suggests that the 0/1h protocol is fantastic, it is the best. As a second choice, you have 0/2h. And as a third choice you have 0/3h. But in reality, the vast majority of the hospitals still use the 0/3h protocol. And why? Because several emergency departments, they say, ”the turnaround... we do the turnaround”. What is the turnaround? The person, the healthcare professional, that has to bring the sample of the troponin... if you have, for example, a two-hours turnaround, then you can't do the 0/1h protocol. Also, this is a mistake because you can collect the sample at time zero, after one hour, and after another hour, and after you have the result, for example, zero and one hour. And you can use the 0/1 protocol for the two-way determination. But there, and also in reality, the overcrowding makes it very difficult to understand when they really do the blood sample. Because, for example, on the computer you can see: the first was at 3 p.m. and another one, you see, was at four (p.m.). But in reality, the nurse made the first at 3:20 p.m. and the second at 4:50 p.m. So, to have the AI algorithm… when you really do the sample... this algorithm that will receive the CE mark, is able to auto-adjust for the algorithm that you are using. For example, to be crystal clear, I'm saying: “I'm going to use the 0/1 algorithm”. But in reality, when I input the time, I slip without knowing into the 0/2 protocol. So when you have the two different results and you are using the 0/1 protocol, the curve is different. In the 0/2 protocol, the same result can bring you, for example, in the rule-out because there are always three outcomes: rule-in, rule-out, and ‘observe’. So this algorithm is very useful because it makes an auto-adjustment. And then another added value is that he does what we do for the emergency department physician because they ask, “When do I have to do the other sample?” or “What time?” This AI algorithm tells you, “You have to do the sample at this time because you are using the 0/1 or the 0/2 protocol. And it tells you… So high-sensitivity troponin together with this, I think in the future they will shape the management of ACS. So I know the time and I am leaving you the floor because when they start to speak... another important thing is when you fall in the ‘observe’ zone, because ‘observe’ is something that is very difficult in clinical practice and in this case...for example, use the cardiac CT for the triple rule-out. 

Dr Sabouret:  We talk only about acute coronary syndrome. But when you look about the advantages of troponin, it's a very validated biomarker for cardiovascular risk, not only in acute coronary syndrome. When you look at all the data... when I saw all the data about troponin, for me, to have a global analytic perspective, we should use these troponins also in primary prevention because as Dr Galati said, it helps to better stratify your risk. And also, after the discharge, after an acute coronary syndrome. Okay, you made the diagnosis of acute coronary syndrome. You treat the patient. The patient is discharged after 24-48 hours. But we issue… when you look at all the data, it may be useful because it's an independent marker of further events at six months, as we said, and also it's in combination with other markers, but it's useful to integrate with new markers for the residual risk. And it's not done in practice. Nobody is performing high-sensitivity troponin after acute coronary syndrome, whereas we have many data to implement these markers to better stratify the risk, as for the residual risk. So it's crucial also to underline this for attendees. 

Dr Segura: Simply, I agree. Final comments… as we were talking about the emergency setting, we didn't mention the great comment that Pierre mentioned. I usually use a high-sensitivity troponin in the outpatient clinic as well to stratify the risk of patients with heart failure or other cardiomyopathies because we know that some cardiomyopathies destroy the myocardium in kind of a way. And the level of high-sensitivity troponin may help us to stratify the risk. So, great comment there. I absolutely agree. 

Real-World Implementation of Gen 6

Dr Segura: I think real-world implementation of Gen 6 is a reality, but maybe, to have a successful implementation, I think it requires cross-functional alignment in the emergency department, cardiology, and ICU laboratory in order to work in local protocols. According to our clinical practice, it depends on every single hospital, worldwide. And I think simplified interpretation is mandatory with these kinds of unique thresholds, eliminating ambiguity between sample types.

Even in the future, artificial intelligence, as you said, may help us to work with what has been done to successfully do that. At the moment. But I think using artificial intelligence with just even one sample and doing this with high-sensitivity troponin with accurate assays, as the Gen 6, may help to get the future done in the present.

Dr Sabouret: We should start with this speech to say that AI will not replace doctors. I don't think so. We would… I don't say for you, but it's a common idea. But AI as doctors, that's not the case. AI will aid doctors to become better. But you need to use this tool in an adequate manner. But it's not... It's not our enemy, it’s our partner. The issue is to use AI adequately as we need to use biomarkers adequately.

Because when you use biomarkers, even for high-sensitivity troponin, for another disease where you have no relationship, it's a misuse. So if we use biomarkers adequately, AI and other tools such as cardiovascular imaging - because AI, it's useful also for CT scan, Doppler echo, etc. - it's our partner that we should use. So we need continuous medical education as we are doing. But we need to repeat messages because even for easy things, like how to implement lipid-lowering treatment, it takes a long time. We should repeat messages. So for troponin, we have an amount of proof about the  specificity as a prognosis marker… But we need to repeat it to implement these biomarkers in real-world practice because you always have a major discrepancy between the level of proof and implementation in the real world because you have a lack of knowledge of the many doctors and healthcare professionals and, independently, of the resources. That's always also an issue.

Dr Galati: Yes. And from my side, what I can say to somebody is that this sixth generation of high-sensitivity troponin, it helps you to stratify the patient in the rule-in, ‘observe’, and rule-out. In the routine, to warrant you a new layer and safer diagnosis. And remember that the case of patients with multiple chest pains. Remember the last chest pain. Okay, in the rule-out, it is very reliable because, of course, in the rule-out, it's very good to have a high-sensitivity troponin because for the healthcare system… and also we tell you, save resources and money, and you give the best at the same time the best treatment to the patient and avoid the patient stay days or excessive time in the emergency department that is overcrowded. And for the ‘observe’ group, the third, that is the most difficult test, Diego and Pierre, not everything  you see is troponin, okay. So you have to differentiate. You don't have to use anymore the word “pathological troponin,” or “non-multiple.” And you have to use high value of the only… at low values of troponin because they are conditions like cardiomyopathy, heart failure, high rate atrial fibrillation, and so on… Chemotherapies, they raise troponin. And this is myocardial injury that is chronic. Or it's subacute differential. You see myocardial infarction to give an impressive rise of the troponin that starts to be seen in less than a few hours and needs to persist for weeks. So also in the ‘observe’ group, this troponin is useful. Of course, AI is a tool to help emergency doctors... of course, It's crucial to teach and train the emergency physicians to understand this about troponin if in the future we will use AI. Of course, it should be stated in the discharge letter that the AI algorithm was used. But of course, for complex cases, there is… the cardiologists… that of course, they call us and we are there for performing imaging tests and so on. So this is my conclusion. 

Dr Sabouret:  And on the last point, but we haven't highlighted enough that maybe I'm running too fast. As for a lipid-lowering treatment or GLP-1 receptor agonists, because I'm always an early adopter. But when you see all the data, for me, troponin should be part of the residual risk evaluation. In outpatients after acute coronary syndrome, not only the first day but also the first month, it helps to stratify better who remains with a residual risk in order to have an optimal treatment, to intensify some treatment or to reinforce rehabilitation or healthy lifestyle. But it's very, in my opinion, very pertinent to perform this troponin also at these times, because in combination with all the markers or risk factors not controlled or insufficiently controlled, it can help you to better stratify the residual risk.

Dr Segura: I think I just commented that it is mentioned.. I think, even with a… no, there are many studies ongoing, but depending on the levels of high-sensitivity troponin, the patient may be classified not only as very high risk but also, for the reason published in the updated dyslipidemia guide, as extreme high risk of cardiovascular events. So, it has not only diagnostic value but also prognostic value, that patient hopefully may survive this acute coronary syndrome. We have to avoid recurrent events.