Please give us a short overview of the most important changes in these new 2022 guidelines.
In our area of the biomarkers, there was really a big change because back in 2014 there was a recommendation to use biomarkers. That means high-sensitivity troponins or NT-proBNP in the peri-operative setting only as a 2b recommendation and that really received more attention and was an upgrade to a level recommendation 1 or 2a, depending on the cases for the use of biomarkers in the peri-operative medicine. And that I think it is put in line with the advances of the use of biomarkers in other areas of cardiology because we’re very used to use biomarkers for myocardial infarction or for acute heart failure. And now they come to help us in the peri-operative setting.
Who should receive risk stratification ahead of non-cardiac surgery and what should be included in the risk stratification process? Which healthcare professionals should be involved in this process?
The key person is, and stays, the anaesthesiologist. They are the ones seeing the patients, evaluating the patients and ultimately also the ones deciding who to get on board as an expert. On the other hand, the guidelines also provide a certain set of variables to find who is a potential candidate for more intense risk stratification or actual cardiac consultation prior. There are time characteristics, so risk stratification is most helpful if there’s elective surgery or at least, surgery which might be time-sensitive, but still offers a period to optimize peri-operative risk.
And then the second question is, is this a big surgery or is this rather a smaller surgery? And especially if it’s intermediate or high risk surgery, then the patient characteristics are important as well. And here we now see the definition of a low risk patient, the intermediate, and a high risk patient, which is dependent on the combination of age and presence of cardiovascular risk factors or even established cardiovascular disease, going from the low-risk patient with no established cardiac disease and no relevant risk factors undergoing a low-risk surgery, up until the category of patients undergoing a high risk surgery, which for example have established cardiovascular disease, which would be the highest risk of patients.
Depending on where your patient falls there are additional recommendations, for example, use of biomarkers like cardiac troponin and NT-proBNP, as well as functional class which we’re all used to use with the metabolic equivalent of at least 4 and then even the guidelines actually recommend to do a multi-disciplinary assessment and therefore a cardiology consultation in the very high-risk patients.
Why is it important to measure baseline cardiac troponin levels ahead of surgery?
I think the main reason here is to have a baseline because we know that with the high-sensitivity troponin, we can have patients that are classified in the group as having a chronic myocardial injury. That means that this patient will have chronically troponin levels above the 99 percentile without dynamic and that’s the baseline and that we know that is related to long-term risk. But the most important is to have a basis is to diagnose an acute change if it occurs after surgery. And when we look at, for instance, the Basel PMI study, we study patients that are over 65 years old with established cardiovascular or atherosclerosis. We can see that almost half of the patient had troponin T-level above the 99 percentile of 14 that’s why it’s so important to have a baseline. It’s like having an identity card, and this will be my troponin identity. So if I was submitted to surgery, I know that I go from this baseline and I can have a parameter to diagnose if that is stable or if that’s increasing.
I also think this identity card is not something that we use for risk stratification pre-operatively as much. There is research ongoing which has shown that troponin adds to, for example, the revised cardiac risk index when considering predictive accuracy, but currently there is no clear management change based on a troponin level alone. So a patient that has been seen and evaluated by an anesthesiologist and has then been cleared for surgery should not have postponed the surgery due to a mildly or slightly more elevation in cardiac troponin if he appears clinically stable.
Could you please describe what peri-operative myocardial infarction/injury is?
The new guidelines now recommend to do a peri-operative active surveillance for peri-operative myocardial infarctions and injuries. So this is a new term which is very prominent in the current guidelines, and which is a term for a situation where you have acute increase in cardiac troponin from pre to post-operative levels, indicating that there is an acute myocardial damage, whether this is by ischemia and therefore termed infarction or by another trigger, and therefore termed injury is unclear at this moment, and needs to be evaluated. But this is why the guidelines use the term peri-operative myocardial infarction/injury. And these patients were previously usually not detected because they present asymptomatic, where we have seen a lot of research that has focused on this specific area and it has shown a clear and robust association with mortality and morbidity. And therefore, you need to be sure that you’re actually treating something that’s acute. Therefore, you need your baseline troponin, your identity card.
Is there guidance on how to identify the underlying pathophysiology and the clinical phenotypes that may cause this PMI?
For PMI, first we have to do a diagnosis. And to that, we have to establish there was an acute raise in the troponin levels. And for this, we need to add a delta of the percentile 99 of the assay used between the pre-operative level, so the identity card and the first post-operative level or second one. And that is, for example, if we consider the troponin T-assay high-sensitivity, the 99 percentile is 14. So if a patient has before the operation 10 and after the operation 25, that will be a PMI.
After we do a diagnosis, we know that that functions completely different than the myocardial infarction at the emergency department. Here we could have several aetiologies. We could have a cardiac peri-operative myocardial infarction or injury that would be a Type 1 myocardial infarction or a Type 2 myocardial infarction, or we could have a non-coronary situation as an acute heart failure, or we could have arrhythmias, like an atrial fibrillation or that all we call cardiac peri-operative myocardial infarction and injury. On the other hand, we could have what we called an extra-cardiac or the primarily non-cardiac peri-operative myocardial injury. And here we have to be clear that that is not a false positive of the troponin. This troponin elevation is coming from the heart, so the heart was injured, but the main disease is primarily not a cardiac disease. And a typical example for this are pulmonary embolism where there is suffering of the right heart, or for instance, a cardiac trauma during a thoracic surgery were the pericardium is opened, or, a septic shock, that would be extra-cardiac causes of PMI.
This is what recent research has actually brought forth on aetiologies. Once you are at the patient bedside, how do you evaluate these patients? The first thing we have to do is go to the patient and make a really good clinical evaluation with a good examination and a physical examination because sometimes this is enough to get a clear situation. If we go there and we see clearly that the patient has an acute heart failure, then we are already in the right track. Then we have of course to make an electrocardiogram to look for signs of myocardial ischemia. That could be even a myocardial ST elevation myocardial infarction that is rare but could happen. Or we can have localized ST-depressions that go in favor of non-ST elevation myocardial infarction. Then we have to think about the haemoglobin of this patient to see if there is a clear trigger. We look for signs of hypotension, not only at the moment, but we look at the anesthesia chart to see if there was important hypotension. During the surgery, we look at the heart rate to see if there was important tachycardia or important arrhythmias that could justify the PMI. And based on all these information, we can make an initial conclusion. We have to act in according to the guidelines, or know that if it is not then we will think about the other aetiologies hierarchically, but always being guided by the patient situation.
Now we have the patient, we evaluated him. Do we need additional diagnostics here? If the case is not clear, if we are not sure we could make an echocardiogram that will help to look for one motion abnormalities to look for valve disease. And with that we can already guide to a certain diagnosis and treat these conditions. If we don’t find anything then we are in phase of a patient that has a PMI and we excluded all obvious cases so we are likely on a Type 2 myocardial infarction. And for these patient, we may need additional testing. What we do in clinical practice normally is assessing the risk of coronary artery disease and determine the patient has already non-coronary disease and then performing search for ischemia in these patients.
What is the importance of PMI screening and what is the mortality that comes with PMI?
I think it is important to also notice potential impact of such a screening. All of the aetiologies just mentioned were associated independently with morbidity and mortality, but we really need to focus on numbers here.
The patients undergoing this surgery, they are of course at an elevated risk, but once you have a PMI, especially for example, a PMI caused by acute heart failure, also tachyarrhythmias, your risk of a follow-up event or mortality is extremely high. So we see up to 50% of patients actually having major adverse cardiac event or death following a PMI, which is for example, of acute heart failure aetiology. Also with Type 1 infarction we of course see about a third of these patients having a follow-up event afterwards and also with of course extra-cardiac triggers like sepsis. This is a very detrimental situation. So finding these PMIs provides us with the opportunity to potentially intervene in this patient’s course, which is going off track. By bringing in this PMI screening, usually these patients have additional safety net, because in a peri-operative setting, there just might be that symptoms are blunted by anaesthesia or analgesia, or attributed to the simple post-operative setting. And then once a bigger event follows suit, it might be too late to actually intervene. So the guidelines have seen this active surveillance of PMI as an opportunity to improve peri-operative care.
What impact will these new guidelines have on clinical practice and how might this influence workload at clinics?
I think the the guidelines will bring major help to the clinical practice because before as Christian said, the importance of the screening is to improve the care of patients in the peri-operative setting. The guidelines came in perfect timing to exactly put together the new troponin assays, the benefit of the screening and providing guidelines to what to do in case of a PMI.
I think the next challenge, of course, will be to implement this in clinical routine. Now, on a practical level, this means that anaesthesiology, cardiology and surgery will intersect more, which means that there needs to be interdisciplinary work and an interdisciplinary workflow. And these workflows are something that has to be established on a hospital level.
Ideally, people who are interested can then reach out and their knowledge should be complimentary here. So the anaesthesiologists will bring all of their knowledge that is already available for pre-operative evaluation and risk stratification, and then combine it with the cardiology approach to actually have a post-operative safety net for these patients, which in turn then can also benefit the surgeons and their outcomes. But on the other hand, the surgeons are the ones who are usually in charge of these patients and who are also the ones that lead the wards where these patients are during their post-operative stay. So getting these three specialty groups together is going to be the center point of actually having an acceptable or a good workflow on a clinical level, which then can be of course even optimized by bringing in an expert from laboratory medicine, experts from IT and hospital management to get such a big project rolling.
Where do you see the pain points to actually apply the guidance in clinical practice?
Helpful is a workflow, helpful is someone who is actually advocating this. And then there’s this new troponin, which for example, would be available post-operatively, might be available pre-operatively. And then there needs to be a certain set of education that an elevated troponin, for example, can be a chronic thing. Troponin assays don’t work as a zero-one anymore since the high-sensitivity troponin assays have been established. We can measure troponin in actually everybody, and therefore a lot of these patients have values which would be considered elevated for a healthy patient, but they aren’t healthy patients, therefore their levels are elevated. This is something that needs to be conveyed to specialists, especially the ones doing pre-op evaluations, but also in the post-operative setting.
Can you talk about the pathway you have in your clinic?
Looking at our institution, we usually do the pre-operative troponin. This can be a troponin which has just been done prior to surgery, but it could also be one or two weeks old. So the pre-op level is done at, for example, maximum of 30 days prior to surgery. On day 1, after surgery, patients usually have a blood draw as well. And if not, then troponin is ordered specifically and these patients let their blood draw between 7am and approximately 9am in the morning. And then we have an IT system behind this that automatically compares this post-operative value to the pre-operative value and gives an email alert to the cardiologist. So this detection is actually automized as far as possible, and the cardiologist then go see the patient. Same thing on day 2. Again, we have a routine troponin drop between usually 7 and 9 in the morning. And again, the system that’s comparing these values at around mid-day and sending out an alert email to the cardiologist then goes to the patient and evaluates them.
What are the unmet medical needs(evidence gaps) when it comes to cardiovascular management of patients undergoing of patients undergoing cardiac surgery?
There are also some questions which are recurring when talking to colleagues about implementing such a screening. One of the questions always bleeding risk in the peri-operative setting. Of course, the base of surgery and after surgery is one where bleeding is increasingly common compared to a stable patient. Now here, it is really important to get a feel for the type of surgery. And here in the beginning we have a lot of discussions with our surgical colleagues where, for example, thoracic or orthopaedic surgery have complete different views on the risk of bleeding or for example, neurosurgery are much more reluctant to start, for example, dual anti-platelet therapy than for example, an orthopaedist simply because of the risk of bleeding in these patients.
But overall, talking to your colleagues is the way to go here, and you get a feeling for when it’s possible to establish dual anti-platelet or oral anti-thrombotic therapy in these patients quite fast. Patients maybe with undiagnosed heart failure with the preserved ejection fraction, these patients tolerate fluids way worse than even patients with reduced ejection fraction and might be symptomatic the first time following non-cardiac surgery.
There is really a lot of gaps in the peri-operative and a big need for research. But I think overall with the new guidelines, our final goal is to give our patients undergoing a non-cardiac surgery a multidisciplinary team approach so that their surgery could go as smoothly as possible and that we can also make diagnosis and strategies to improve short and long-term survival in these patients. And I think with these new guidelines, we have now tools that we can already do a lot for our patients.
