Recorded at the 6th McMaster International Review Course in Internal Medicine.
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Professor Roman Jaeschke: Good morning, good afternoon, or good evening. I welcome you to the second question and answer session of McMaster International Review Course in Internal Medicine. My name is Roman Jaeschke and I am one of the organizers. And if everything works properly, I should be visible on your screens at the moment. We just finished the first session. I want to remind everybody that every Thursday we will have two meetings – one at 17:00 Central European Time or 11 a.m. Eastern Standard Time – with the panelists who presented their lectures during the previous day. I would like to welcome today at least three panelists whom we have at the moment, who have joined us. We are waiting for the fourth one. I would like to introduce to you Professor Reinhold Kreutz from Berlin, Germany. Professor Kreutz is the president of the European Society of Hypertension and his lecture dealt not only with COVID-19 and hypertension, but all aspects of COVID-19 involvement and the effects of that disease. We have Professor Adam Torbicki from Poland. He was the vice-president of the European Society of Cardiology and one of the main authors of the consecutive practice guidelines for the diagnosis and management of pulmonary embolism. Last but not least, Professor Stephan Haulon from France. And the unusual characteristic of Professor Haulon is that he is a surgeon. And I would say, I listened to his lecture completely flabbergasted and amazed. It sounded like science fiction completely to me, as an internist. And I enjoyed it immensely. We are missing at the moment Professor Potpara from the University of Belgrade, who is a specialist and an author of the European Guidelines on Atrial Fibrillation Management. I hope she will join us; if not, I will put [in a] few calls to my colleagues at McMaster University in Hamilton. If not, we will have two options: either we will answer those questions – which may be a little unfair, looking at your specialties – or I, as an internist, will tell you what I do, which may be quite useless. Or we will record the answers of Professor Potpara and we will attach them to this session. So I would like to introduce to you our speaker and maybe everybody could wave – Professor Haulon, Professor Torbicki and Professor Kreutz. So maybe we will start by going with Professor Kreutz here. And the questions – I just want to remind our participants that you can add questions using the “questions and answers” tab at the bottom of your screen. [There is a] question regarding COVID-19 and that’s how we will start. We have this new condition of chronic COVID-19, or long COVID, or persistent symptoms of COVID-19. And a big part of that is obviously dyspnea, fatigue, maybe cough. The question from our participants is when to suspect heart failure and how would you approach investigations rather than dismissing it [and assuming it] will go away after 12 weeks?
Professor Reinhold Kreutz: Thank you. Obviously a very important and good question. For me, The path of long COVID obviously is a kind of a black box up to now, summarizing different symptoms, including fatigue, which is also very difficult clinically to evaluate. I think first, it depends on the patient and the post-COVID-19 situation. Certainly, if the patient due to the acute course of disease had some cardiac involvement, [then] obviously follow-up is much more important and, you know, the likelihood of having heart failure is also much more important – even though we do not know the different phenotypes. I am not talking now about patients who have like a classical myocardial infarction – which could also be a coincidence – but maybe a patient who had this unspecific kind of cardiac injury during COVID-19 in response to the cytokine storm or inflammatory response syndrome or the patient was just detected by having an elevated troponin level. I think the first issue depends on the likelihood and the need to do further investigations of follow-up based on the acute course of the disease. So it’s very important to read… if the patient has been discharged, we look very carefully at the diagnosis and the discharge letter, including all parameters. On the other hand, if the patient develops fatigue without having had acute cardiac injury due to acute [form of] disease, I think clinical judgement and physical examination always comes first: careful clinical investigation, judgement, and looking for any signs of heart failure. And then this next step obviously is for further investigation, starting with biomarkers, BNP, and the first investigation that should follow up – in addition to ECG – would be echo really, I think. And so it’s an individualized approach, but I think we should not – with this many patients labelled with this kind of fatigue syndrome, I think clinical judgement would be very important. Also obviously, if you also mention dyspnea and cough, obviously respiratory involvement, I mean, the follow-up is very important. And we know that dyspnea and impaired exercise capacity, you know, is a classical phenomenon in these patients after having had acute COVID-19 disease. But with regard to heart failure, I think clinical judgement first. [For] patients without acute cardiac damage due to disease, clinical judgement first and then biomarkers and echo, and obviously, always, ECG is also [].
Roman Jaeschke: So, [it’s] a similar approach as you would [use] outside the COVID-19 era, so to speak. And maybe a question to all our panelists who would like to take part in answering: On the basis of the information which we have, should we treat presentations of COVID-19 somehow differently than we treated the same cardiac or cardiovascular complications outside [of COVID-19]? It may be hypertension, it may be thromboembolic disease. I’m not sure how to fit aneurysm into it, but maybe Professor Haulon will have something to add as well. Or is it all the same?
Professor Adam Torbicki: Well, if you mention thromboembolic disease, I must say that following what Professor Kreutz said, we have a lot of patients referred to us with the suspicion of post-COVID-19 pulmonary embolism, and we have to treat it very seriously because indeed, this is a risk factor. And those are patients that come with, let’s say, dyspnea or fatigue syndrome, but have elevated D-dimers. And this is what brings a particular problem here, because sometimes the symptoms are not that related to something that we would suspect to be pulmonary embolism, but those D-dimers are persistent and sometimes quite high. And what [should you] do, start a full diagnostic procedure with CT angiography, and so on and so forth? Or just perform venous ultrasound to see whether there is something still there which can result in pulmonary embolism? Our common approach is that this episode of COVID-19, which is clinically relevant and may bring the patient to the hospital at that time is thrombogenic, but afterwards, it usually tends to disappear. So COVID-19 is one of the diseases which should probably be considered for three months’ anticoagulation. And then stop. So if this was not diagnosed during the COVID-19 infection but suspected later with not very specific signs and symptoms, we have a problem here. But of course, the question was slightly different: whether we should treat differently patients with pulmonary embolism who have COVID-19. Not very much. I think the treatment is more or less the same. COVID-19 does not induce too much hemorrhagic risk. So we are here on the relatively safe side. And we have to go according to the general lines of the guidelines.
Roman Jaeschke: Let me follow with the investigations. And as you volunteered to answer first, the next question comes to you as well. In your lecture, you beautifully presented the pathway based on D-dimers, CT scans, CT angiography and so forth. We have listeners from 60 different countries of the world. And the question is – and I’m not sure whether you can contribute to it – say that you are practicing in northern Canada. You don’t have CT angio, you may well not have D-dimer. What would you advise such a person?
Adam Torbicki: Well, this brings me back to my years when I was a medical resident or even a medical student. And we were more or less in this situation, even working in the big city and the medical university. And what I may say is that unfortunately we found a lot of errors in our clinical approach to those patients when the only diagnostic tools were classical angiography or lung scintigraphy, which were very poorly available. And we had a lot of failures which we detected at autopsy. So it is not a very nice situation not to have diagnostic tools when you are faced with patients suspected to have pulmonary embolism. And as you all know, the signs and symptoms of pulmonary embolism are extremely non-specific on many occasions. So what can I advise to somebody who doesn’t have CT and doesn’t have D-dimer? Well, try to have access to a center which can make the diagnosis, and in the meantime, if the patient does not have contraindications to anticoagulation, try to protect him for 12 hours or 24 hours, which is required to transfer the patient to a place where you can complete the diagnostic evaluation. If you feel that pulmonary embolism is really something that has to be suspected. I would like to remind you that there is the so-called PERC score. It was developed in the United States some 8 years ago, which can in a way disintegrates the clinical suspicion of pulmonary embolism and allows you not to treat and not to proceed with further diagnostic tests in patients in whom somebody suspected pulmonary embolism, but it is not justified by the clinical picture.
Roman Jaeschke: Well, thank you. You know, I will direct the next question to Professor Haulon, but what strikes me is that we frequently have those discussions. And I remember having my colleague from one of the different countries who said, “you guys keep talking about choosing t-PA versus streptokinase to thrombolize, or not to mention even putting stents [in]; we would like to give each of our myocardial infarction patients aspirin” – because they don’t have access to it.” And the reason why my next question is for Professor Haulon is [that] I was looking at these futuristic CT scans which were rotating around the patients and 3D models of an aorta were shown with an insertion point of every possible artery. What you do is quite incredible. How common is it in the world, what you are showing us?
Professor Stephan Haulon: Thank you very much for your question and for inviting me to participate to this great meeting. Let me just add something to the previous discussion, if I may. I just want to add that we’ve actually found a lot of thrombus in the aorta, in patients that had CT scan for elevated D-dimers, for pulmonary embolism. And the PE [pulmonary embolism] was ruled out and we found a lot of patients with major thrombus in the aorta. Most of them, fortunately, were without any clinical symptoms and we treated them only with heparin. But in other circumstances some patients had to be treated and went to the OR to have thrombo-aspiration or open surgery. And the very high risk in those patients, if it is during the high inflammatory period, is that they re-thrombose after the procedure. So those are very difficult patients to treat. Most of them were young patients with undiseased aortas. And what we found is that there was this major inflammatory response, also from the aortic wall or the arterial wall. So it was a strange time for us and not the usual ICU patient coming in for vascular surgery. So sorry, this was just to add to the previous discussion. Now, thank you for asking regarding 3D imaging. What I can tell you is [that] for the last 10 years, my work has changed every other year because of what the imaging industry has provided us and also what the endograft industry has provided us. So we now have, with the [latest]-generation hybrid rooms, the opportunity to do what you were describing, which is a 3D rotation around the patient which will provide the CT-like images. We call that the cone-beam CT. I would say that in most high-volume tertiary referral centers throughout the world, those hybrid rooms are available and most vascular surgeons or CT surgeons or cardiologists or interventional radiologists have access to this technology and it’s becoming more and more routine. The same question 5 years ago would have been, “well, not that many people have access to this type of technology.” And 10 years ago, “there are a couple of centers around the world.” So this is really changing quickly. And I had the opportunity to come and perform a couple of cases in Poland and my colleagues in Poland also have access to this technology.
Roman Jaeschke: That’s fantastic. Again, for a simple internist and intensivist, it still sounds like science fiction. It was, I was looking at it as a very good movie, actually, you know? On the edge of my seat. Thank you for presenting it to us.
Stephan Haulon: It’s very interesting because now that we have access to this technology, our mindset has completely changed. And obviously, we are now pushing the envelope now that we have the opportunity to have custom-made devices that can fit perfectly the anatomy of each patient. So, most of those devices will require 4–6 weeks to get manufactured, but then they will perfectly fit to the patient’s anatomy. And this is why with the guidance of 3D imaging, we can obtain good results. And obviously, not requiring a pump or a sternotomy to repair an arch aneurysm [is] a huge benefit for the patients.
Adam Torbicki: May I add something to this? We are using this for pulmonary circulation because this is so complex in terms of topography and to extract chronic organized thrombi from the pulmonary arterial bed or [to] perform balloon angioplasty, it is of great importance. And it really works. So I support this trend towards 3D reconstructions. It’s – particularly in pulmonary circulation – it is extremely useful.
Roman Jaeschke: It looks like a new art as well. A follow-up question for Professor Haulon and maybe to Professor Torbicki as well: what are the complications of putting [in] those complex foreign body inserts? – a question from the audience.
Stephan Haulon: I think it’s a great question because obviously, when we’re treating those patients with open surgery, you cannot end the procedure [and] close the patient with a leak, because otherwise the patient would not survive. But with the end of vascular procedures, if your endograft design is not correct, you might not get a proximal or distal seal because the idea is to get a seal above and below the aneurysm. So that is why you need to follow up the patient with CT scans or duplex ultrasound, depending on the location. The arch or the thoracic aorta requires a CT scan or MRI, whereas the abdominal aorta can undergo ultrasound surveillance. Now, there is another type of endoleak which is type II endoleaks from the collaterals of the aorta, so the intercostal or lumbar artery can back-feed the arginine cycle. And most of those type II endoleaks are low-pressure, low-flow, so they are not associated with any bad outcome, I would say, so we usually just follow them.
Roman Jaeschke: So if you co-perform this procedure, again a question from the audience, how often should you check with your ultrasound in case the patient is asymptomatic?
Stephan Haulon: So usually when the patient is discharged after an ultrasound, after a couple of days in the hospital, then we would get the patient back for a consult with the CT scan 2 months after the procedure. The next follow-up would be 1 year after and usually we would do a CT scan again. If there are branches to the visceral vessel or to the supra-aortic trunk, we would do ultrasound as well. And then, if everything looks good, usually we tend to restrict to only ultrasound to avoid excessive exposure to X-rays and to contrast media.
Roman Jaeschke: Thank you very much. Professor Kreutz, a few questions about [the] treatment of blood pressure post-COVID-19. The first one was about the use of loop diuretics: In your lecture, you mentioned that no other class of drugs seems to be detrimental, but loop diuretics possibly. Would your pattern of practice be changed with that?
Reinhold Kreutz: Thank you for the question. No, I don’t think so. Most likely, I think in particular… in a study by Professor [00:23:23] from Milan, there was an increased hazard ratio associated with loop diuretics. Also in some other studies. And that could be actually pretty confounding by indication, I think, I would say, from the methodological point of view, because if loop diuretics are used in a proper way in cardiovascular disease in patients with advanced kidney disease, edema, or severe heart failure… in terms of treatment of higher hypertension of blood pressure, maybe I can use the possibility to discuss this topic in general: loop diuretics are not antihypertensive drugs. So they have not been tested and we recommend them certainly down to eGFR of 45 mL/min. Thiazide or thiazide-like drugs, these are the antihypertensive drugs. We very often see patients come in with severe hypertension [being] treated with loop diuretics, even though they do not have an indication for loop diuretics. Because they are not good blood-pressure-lowering drugs. So if you have an eGFR below, let’s say you can consider 45, definitely 30 mL/min, you may use loop diuretics. You need to use loop diuretics, but other than that, you should treat [with] thiazide [or] thiazide-like diuretics. And again, the risk associated with loop diuretics [is] possibly due to the more advanced disease in those patients with heart failure and also advanced chronic kidney disease.
Roman Jaeschke: A question from a different viewer: Do you think the control of blood pressure is more difficult in patients after COVID-19? Do we need to increase the dosages?
Reinhold Kreutz: Possibly, several reasons why the blood pressure control in patients post-COVID-19 could be impaired, or in the post-COVID-19 era, because, you know, lifestyles changed, diet, salt intake, alcohol intake. So those lifestyle factors that contribute to hypertension may be changed in an unfavorable way, including salt intake [or] alcohol intake. We have observational data on this. In terms of pathophysiology, I think I’m concerned about endothelial damage, [which] in those patients during acute COVID-19 disease and post-COVID-19 actually might contribute to endothelial dysfunction and also hypertension. That could be actually a pathophysiological aspect that could contribute to impaired blood pressure control and support the need for increasing [dosages]. So basically, we should intensify blood pressure monitoring in those patients during follow-up and also check whether those lifestyle modifications [are made], also [including] reuptake of physical activity after lockdown, is very important.
Roman Jaeschke: OK. I will have more questions, we do have more questions about blood pressure, but maybe I will ask Dr. Haulon now something which is much simpler about what he does. But it was a question from one of our listeners. What is current practice, at least in Europe – or maybe we will see something more – about the screening for abdominal aortic aneurysm? You were showing us rare cases of thoracic or arch aneurysm, but more common is probably abdominal [aortic aneurysm]. What would be your recommendation in this area?
Stephan Haulon: So this is correct. Abdominal aortic aneurysms are the more frequent aortic aneurysms. I fully agree. The screening programs are really… there is a real benefit and there has been a lot of literature showing that you will reduce the cost associated with aneurysm repair and increase [the] patient’s life by performing screening. But it has a cost associated with it, so not all countries tend to perform screening. As far as I know, Nordic countries and England are quite good at performing this AAA screening. We in France don’t do it, which is obviously wrong, and I’m not sure about Canada or Poland. I’m not sure that this is something that is routinely performed. But if you summarize what is in the literature, there is a benefit of doing it in male patients over 55 [years old], especially if they are smokers.
Roman Jaeschke: Thank you. I think that’s what is suggested in Canada and I think it goes anywhere from 3 to 5 years. It may change with the advance of endovascular treatment, which is, you know, so much simpler than abdominal aortic aneurysm resection. Professor Torbicki? But you need to unmute.
Adam Torbicki: Yes. I would like to address this issue of aneurysms, aortic aneurysm. I wonder whether you have any experience with pulmonary artery aneurysms. And we are following a lot of patients with pulmonary hypertension who develop pulmonary artery aneurysms and the outcome may be very similar to what is happening with aortic aneurysm, especially proximal. You may have dissection, you may have cardiac tamponade, and this is largely ignored. So I wonder whether you have ever seen such a case and have been involved in the management decisions?
Stephan Haulon: Thank you very much for your question. It is actually; I work in a center called Marie Lannelongue near Paris, where my colleagues have huge experience with chronic pulmonary embolism and we also do a very high number of angioplasties. And so we follow a lot of patients. I am not an expert in that specific field, but we have discussed a couple of cases with pulmonary artery aneurysms. And the indication for treatment is unclear because, unlike AAA, where we have a prospective randomized trial that nicely shows that once the AAA is larger than 55 [mm], there is a real benefit of treating the patient. It is really unclear for pulmonary artery aneurysms when to treat them, when they are at risk. I fully agree with you, some of them will get complications – and you’ve described nicely all those complications – but we tend to be not too aggressive with the pulmonary artery aneurysms. [In] the last 4 years, I think, we’ve treated 1 that was really huge, if I remember well. It was almost 60 mm and there were other issues with it, but it is really not routine, although we are a center that treats a lot of patients with pulmonary artery issues. I don’t know if it’s the same in your practice, but it seems that the thoracic and CT surgeons are not very excited about treating those pulmonary artery aneurysms.
Adam Torbicki: Yes. I don’t want to go on with this because it’s rather a narrow area and Professor Jaeschke will be angry with us that we discuss this and not things which are more popular.
Roman Jaeschke: Well, we still have some questions and you have each other’s email [addresses] now, so maybe we could return to it later. I am thrilled that the surgeon is so popular. It’s a tribute to the multidisciplinary aspect of today’s medicine. But let me stay on the topic of hypertension and aneurysm because it’s all connected. Professor Kreutz, a question which is again simpler, I think. You are, I believe, the president of the European Society of Hypertension. We struggle with the threshold at which we are aiming – 140, 130, 120 [mm Hg]. Numerous practice guidelines [are] telling us something different. What’s your approach to it?
Reinhold Kreutz: Yes. I am not happy with this discussion because I think it is kind of confusing to the general internist and GP. We are reaching out now, trying to have a more general consensus. And maybe I should not add to this, but there is a recent The Lancet meta-analysis, just published last week, which contributed to the confusion, which I do not like because it suggests that you don’t even need to measure blood pressure, just use blood-pressure-lowering drugs to reduce the risk. And even down to starting treatment in patients where the blood pressure is less than 120 mm Hg, which is very, you know… we are a little confused by the meta-analysis and these people doing this large meta-analysis – sometimes it’s a black box for me. But nevertheless, I think we in Europe and also the International Society of Hypertension still maintain also the WHO definition of 140/90 [mm Hg]. And rather than the meta-analysis, I’m in favor of looking into distinct, primary, original trials that address the question. A crucial question was the HOPE-3 trial – recently conducted, I mean in 2016, by Dr. Salim Yusuf from your institution, your area – really showing [that in] a low- or middle-risk patient blood pressure lowering does not add any benefit if you are not hypertensive according to this definition, 140/90 [mm Hg], even though it was kind of secondary analysis. With regard to targets, I also think there is a lot of evidence showing that we have a safety threshold [where] treating and lowering blood pressure actively with drug treatment below 120 systolic and 70 mm Hg does not add benefit, maybe it adds, if anything, harm. So I think I’m still convinced on the data we have from many trials suggesting this: Ontario trials, other trials. So basically we are aiming for… We have a meeting in September coming up, to try for the future, pave the way to have a more global consensus on this. It’s difficult enough to control blood pressure below 140/90 because many patients are not controlled, so I support the definition [of] 140/90 and patients should be below 140/90. If they are younger, and younger is less than 65, you can target down to 130, in this range or even lower.
Roman Jaeschke: I hope even this threshold will prevent some of the abdominal and thoracic aneurysm, not to mention pulmonary artery.
Reinhold Kreutz: Yes, that’s a difficult issue. I mean, one of the indications where really strict blood pressure control is of utmost importance, is those patients… if you know, [as Stephan said] it’s impossible to operate for whatever reason, you know? It’s difficult. And in prevention, I think the lower, the better for these patients. I mean, they are one specific or unique population where blood pressure control is very, very important, really.
Roman Jaeschke: Yes, Professor Haulon?
Stephan Haulon: Yes. I fully agree, especially for patients with dissections. This is mandatory. And I think I want to echo what you were saying previously. It is a multidisciplinary approach for those patients with aneurysms and dissections. Repairing the aorta is just one step of dealing with the disease. And we work very closely with cardiologists, we work very closely with internists, or “vascular doctors” as we call them in France. And repairing the aorta is just one step of the treatment of the patient, because before and after, there is a huge need for a follow-up with a cardiologist and internist.
Roman Jaeschke: Well, that’s an amazing multidisciplinary discussion. I’m really enjoying it. Related questions for Professor Torbicki at the moment – two actually. The first one may be easier: You mentioned ventilation/perfusion scan as part of your youth. Is it obsolete these days? It is being used? Does it have a place?
Adam Torbicki: Well, it definitely disappeared a little bit from our clinical practice, but it is not really justified because this is a very good test, especially to exclude pulmonary embolism. And here you can even use only a perfusion scan. And this is a good approach, for example, in pregnant women who refuse to be tested by CT, which is maybe not quite justified but for psychological reasons sometimes it is very difficult. So perfusion scan is excellent for excluding pulmonary embolism, even better than CT. A VQ scan can be even more useful clinically if it is performed in a more modern way with 3D reconstructions, and 3D reduces a lot of inconclusive results of the scan. The problem is that, usually, access to this type of diagnostic tool, at least in Poland, ends [at] about 1 p.m. And in the afternoon, you cannot have this tool and you cannot use it, also during weekends. The nuclear labs do not operate very long. And CT is so easily available that it prevails in our clinical practice. But certainly, there is a place for VQ scintigraphy. If you know the algorithm, it has its place there in several clinical circumstances.
Roman Jaeschke: Thank you. The second question is not only for you, but for all of us. And the reason is that I suspect there are no answers coming to us from the usual high-quality sources. COVID-19 people have a tendency for thromboembolism, obviously. Everybody who is admitted to hospital, I believe, will get thromboprophylaxis at least. But at the same time, there is a whole discussion about anticoagulating people admitted, especially with a milder form of disease, to the hospital. And there is a whole number of people who are treated at home, even using, you know, oxygen supply, even if they are mildly hypoxic. Oxygen supply and [an] oximeter at home and whatever medications given place and beliefs, are worthwhile. Should we think about prophylaxis for thrombotic diseases in out-patients with COVID-19? We will have a session on hematology and COVID-19 will be part of it, but I’m just curious and at least a few of our listeners are curious what we think about it. Any opinions?
Adam Torbicki: Well, I should probably speak about [this] as I am supposed to deal with venous thromboembolism. Well, as in other situations, there is a continuum, so some people who stay at home are in fact more sick than those that are hospitalized. So I would say that definitely we should think about it, also because when something happens at home, and by this I mean a pulmonary embolic episode, it is much more dangerous than if it happens at the hospital, where you have immediate diagnosis and immediate treatment. So though we don’t have evidence, I would certainly support at least considering thromboprophylaxis in those patients [who] remain at home, but have symptomatic COVID-19 with reduced oxygen saturation, with signs of important disease. But I repeat, [there are] no data; I think there is a report of 72 patients [and] some of them reported to the hospital very early after staying some time at home, and I think something like 20% of them were found to have pulmonary embolism. So I think the problem is there and I would be relatively supportive of the option of thromboprophylaxis.
Roman Jaeschke: Obviously, it’s difficult to operationalize. Professor Haulon?
Stephan Haulon: I just wanted to add [that] in our vascular patients, we’ve had to be much more aggressive than before, especially for those patients with COVID-19, but also we have had much more occlusion of bypasses and any type of repair, like stenting of occluded iliac arteries. Because the range of patients coming back with occlusion has increased and you realize that the patient had COVID-19 weeks or months before, and suddenly occluded an artery they shouldn’t be occluding. So we’ve been more aggressive – and also in those patients that are really in bad shape due to a very aggressive form of COVID-19, when we need to position ECMO lines, we are actually giving much more heparin than in usual ECMO patients because otherwise the ECMO lines occlude. And so we’ve completely changed the way we use heparin and the way we discharge the patient during this COVID-19 period.
Roman Jaeschke: Well, let me ask a related question on [the] use of anticoagulation in different forms. And it was actually a question for Professor Potpara in relation to atrial fibrillation. And again, I don’t think we will venture into most of the questions directed to her because we may provide wrong information. I promise that we will submit the questions to her and we will try to record her answers. But the general question is as follows: We keep anticoagulating more and more people, for a variety of reasons. And the question is [about] the follow-up medications, which are proton pump inhibitors. Obviously, any anticoagulation – starting from aspirin through everything else – will increase the risks of bleeding. In your own practices, do you have a pattern of giving or not giving protection from peptic ulcer disease? [Does] anybody want to take a shot at this? … Well, it doesn’t look like we have a volunteer.
Reinhold Kreutz: As a clinical pharmacologist, and also, I’m interested in atrial fibrillation. I mean, first of all I think generally the recommendation is we should not use PPIs [proton pump inhibitors] unless we have a clear indication. We see many patients of chronic treatment [with] no clear indication to use PPIs and there may be long-term negative effects. On the other hand, patients at a very high risk of bleeding, upper GIT bleeding possibly would justify, would be qualified for this. A classic example from my point of view is a patient anticoagulated, a high risk of upper GIT bleeding, using antidepressants. You know, the SSRI inhibitors, for instance, increase significantly, up to 2-, 4-, or 5-fold the upper GIT bleeding risk because of their mode of action. And that can be almost eliminated by the use of PPIs. So this is just one example in terms of complex structure. So a patient with a history of upper GIT bleeding or high bleeding risk, that’s one of the reasons we can use the [00:45:50] scores – not because we can modify all these parameters, but it reminds us about the bleeding risk – and if you have a high upper GIT bleeding risk, particularly I think I would encourage, in the very elderly particularly, [the] use [of] a PPI. Patients with acute coronary syndrome, you know, atrial fibrillation, using dual or triple therapy – depending on the cardiologist’s recommendations – that the high risk, for this high risk situation with double or triple therapy, I think also PPIs could be used. And there is some guidance in the cardiology guidelines when to use PPIs in these patients. So I would encourage but generally I would discourage [the] use of general PPI use, but in these patients – [with] a high risk of upper GIT bleeding, I think [in] many instances we can use it in a proper, responsible way.
Roman Jaeschke: OK. So obviously, the higher the perceived risk of bleeding and higher intensity of anticoagulation or [00:46:57 – problem with the connection] treatment, then the PPI may make some sense but not…
Reinhold Kreutz: A classic patient, sorry, with depression and using these SSRI drugs. And you know, because they double the bleeding risk, particularly GIT bleeding, and you can eliminate this with PPIs.
Roman Jaeschke: Well, I learned something new for sure. Professor Torbicki, yes?
Adam Torbicki: In venous thromboembolic disease, if you decide to treat the patient longer, beyond 3 months, there is an option of reducing [the] NOAC dose for those drugs by half, after 6 months of treatment. So if you perceive that the risk of bleeding from the GI is high, you can keep this protection for 6 months and then get rid of it. And of course, when we have additional anti-platelet therapy, we usually try to cover this period with gastric protection in patients who receive anticoagulants.
Roman Jaeschke: OK. I just want to mention for our listeners at the moment, the scope of questions will be [larger] once we have contact with our expert [in] atrial fibrillation. We will be talking about how often to monitor people who are taking amiodarone, which tests to perform in such people, [and] how often [to] monitor patients with atrial fibrillation in terms of the need for anticoagulation. We’ll be talking about the role of aspirin in [the] prevention of strokes in people with atrial fibrillation. We will ask again the question of proton pump inhibitors. And we’ll talk about pharmacological cardioversion, which drugs are acceptable or preferred, or what is the pattern of practice at least. So again, I don’t want to venture into it because we may provide wrong answers. So I will stick to our experts’ expertise. And still, a question for Dr. Haulon which is two questions, in fact. Is there… aneurysms, my suspicion – unless they are sought after – are detected incidentally, either on X-rays or echoes or CT scans or what not. When [should we] refer to you?
Stephan Haulon: I think a really high majority, 95% of aneurysms are depicted, fortunately, before they rupture. And so those are the aneurysms we can fix. Because if a patient ruptures, you know, for those who will arrive at the hospital, maybe 40% will die, but if you look at all the ruptured aneurysms, it’s probably above 80% that actually die after a rupture. Now, we have two main reasons for having a treatment scheduled. One is if the maximum diameter of an abdominal aortic aneurysm is greater than 55 [mm]. The second one [is] if there is rapid growth, being defined as more than 5 mm in 6 months or more than 10 mm in a year. So what was called “a small aneurysm,” between 45 and 55 [mm], will only get fixed if it is associated with rapid growth. Other than that, it is very rare that we operate on small aneurysms because usually they are completely asymptomatic and it’s very rare to have an aneurysm with intraluminal thrombus that will embolize to the limb and be responsible for lower limb ischemia. So I think we mostly refer to the diameter. And what is good is to perform the follow-up only on ultrasound and perform a CT scan only when the patient has an aneurysm larger than 55 [mm].
Roman Jaeschke: Well, thank you very much. That was a decisive answer. The second question, actually the third one, is for you as well. We learned today from Professor Kreutz that SSRIs are doubling the risks of bleeding. There is a question which I wasn’t aware of. Is there an increased risk of dissection of aneurysms related to [the] use of quinolone antibiotics? You know, are you aware of it?
Stephan Haulon: So there are some data – and this is not high-level evidence supporting that quinolone may be associated with a higher [growth] rate of aneurysm – but it is really not something that I can certify today. It is really not crystal-clear.
Roman Jaeschke: Alright. And the last question for you. You mentioned anatomical contraindications to endovascular treatment. Could you give us one minute on that? Any other contraindications?
Stephan Haulon: Sure. I think that the idea first is to look at the anatomy and look at the physiology of the patient. [In a] young patient with connective tissue disorders such as Marfan or Loeys–Dietz, we prefer to make an open procedure because we are 100% sure that the long-term outcomes will be better, because there is always a risk of a secondary procedure with the endovascular procedures. Now, when looking at the endovascular approach, I mentioned earlier that we need a nice landing zone. So if you want to use an off-the-shelf design, a standard design, you need to have at least a neck of 15 mm below the renal arteries when treating AAA. If you don’t have this neck and if the neck is larger than, I would say 31–32 [mm], then you need to move to the custom-made designs that I was quoting in my talk with fenestration of [a] branch because you need to move the proximal landing zone above the renal and vesical arteries. So this is basically what we are looking for: a long, non-diseased proximal and distal landing zone, in order to reduce the risk of a secondary procedure during follow-up.
Roman Jaeschke: Well, thank you very much. We are approaching the end of our allotted time. Professor Kreutz, Professor Torbicki, Professor Haulon – any questions for each other? Go ahead.
Adam Torbicki: Maybe this is not a question but a plea. And it is related to systemic hypertension and to pulmonary embolism. It is very common that patients suffering from acute intermediate risk or even high risk or close to high risk pulmonary embolism previously had systemic hypertension. And before they reach us, those drugs are not discontinued. Sometimes those patients [are still receiving] them and they deteriorate because lowering the systemic blood pressure reduces the coronary perfusion gradient to the right ventricle. And of course some of them, like beta blockers or calcium channel blockers, reduce inotropism of the right ventricle. So I would like to ask our listeners to consider this. And if the patient suffers from acute PE and his blood pressure is lower than usual, please discontinue his or her antihypertensive drugs, because this will increase their chance of survival.
Roman Jaeschke: Well, thank you for this. On that topic I want to thank you for teaching me and I hope I’m not the only one who learned quite a bit today from each one of you. I have to say that the most rewarding is to hear from the President of the European Society of Hypertension that this threshold, the target for high blood pressure, is not clear, or at least it’s controversial. So I’m not missing something big and I do not need to be anxious, which is the major outcome for me. So that’s fantastic. And I learned from Dr. Haulon when to refer and again, this will reinforce what I do and I am more apt to use age-adjusted D-dimers these days. And now I understand why my colleague, whom I sent to [the] emergency room a few days ago with a D-dimer of 580, was not investigated: because 600 would be the threshold. I hope we all learned from it. It was fascinating for me to listen. I truly enjoyed it and I hope I am not the only one. Thank you very much.
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Roman Jaeschke: Welcome to Professor Tatjana Potpara from Belgrade, Serbia. This is a recording for the question and answer session. I first would like to congratulate [you] on [an] absolutely fantastic review of atrial fibrillation. And we received a number of questions. Maybe the first one, not necessarily in order of importance. Professor Potpara, you mentioned long-term maintenance of sinus rhythm with a number of medications. They included amiodarone, dronedarone, flecainide, and propafenone. How do you monitor the efficacy of these drugs and how do you monitor for potential side effects, specifically for amiodarone?
Professor Tatjana Potpara: Thank you for that great question, which is of great practical relevance indeed. There is no one-size-fits-all algorithm for patient follow-up, but it depends on the overall patient risk profile. Nevertheless, there is a general rule that patients with first diagnosed atrial fibrillation should be seen within the first month following the diagnosis and first treatment and then regularly, at least once or twice yearly. It is expected that patients would be seen by their GPs even more frequently for refills, prescriptions, and other reasons. So the recommendation would be to take a careful history for syncopes or palpitations and to take an ECG to monitor for a prolongation of the QT interval and so forth. [It] is also important to monitor blood electrolyte levels and to make sure that there is no derangement there.
Roman Jaeschke: Any need to monitor, for example, a thyroid function test?
Tatjana Potpara: As for amiodarone, indeed, there is. And again, there is no high-quality data to guide clinical practice. But speaking from my experience – because [I’ve been] using amiodarone for almost 30 years now and in thousands of patients – if you look at thyroid hormone blood levels every 6 months, then your patient would be absolutely safe. You will be able to catch the change [in time].
Roman Jaeschke: OK. Alright, so that’s your pattern of practice. Now, the other issue was monitoring the patients for bleeding risk. And my understanding is that those who are at high risk of bleeding also usually have high risks of stroke. What is the practical advice to physicians who are to do such [follow-up]? What should they really be concentrating up on?
Tatjana Potpara: Yes, there are two important aspects. First, if we look at patients with first diagnosed AF, it has been observed that a very high percentage of such patients, as high as 80%, will develop clinically overt cardiovascular or other medical conditions within 6 months of the first diagnosed atrial fibrillation. So it is very important to see the patient – even if [they are] apparently completely healthy – with the first episode of atrial fibrillation within the next 6 months, because at the second visit the patient may not be healthy any longer. So speaking about first diagnosed, apparently low-risk patients. As for those at [an] increased risk of stroke, they will be prescribed all-anticoagulant therapy. So the rhythm of follow-up, at least for blood tests and coagulation tests, will be determined solely by the nature of the drugs prescribed. Patients prescribed vitamin K antagonists will have to be monitored within the first week and then every 3–4 weeks, to monitor for the vitamin K antagonist’s anticoagulant effect. As for patients prescribed NOACs, of course the rhythm of clinical and lab visits will be determined by the patient’s individual risk profile, but in general – once we prescribe an NOAC, we must not forget the patient, even [one] with apparently low risk. The next clinical follow-up should appear within a month. And then, the frequency of follow-up visits will depend on renal function and the patient’s overall risk profile. And though [it hasn’t been] tested in a trial, there is an approach [where] you take the glomerular filtration rate value, divide by 10, and you know your interval [in months of] when to see your patients. For example, if the GFR is 30, then it means that you should see your patient on an NOAC every third month.
Roman Jaeschke: Right. Now, we, in terms of NOACs, one other question. Do you use the same dose for most patients? Is there a rule to modify the dose depending on the risk? Is the dose constant or can we say “OK, we will use 1/2 or 3/4”?
Tatjana Potpara: Yes, [that’s] a very important question. Thank you so much for that. Repeatedly, not only randomized trials, but also large observational data sets have shown that optimal dosing is associated with best outcomes – patient outcomes with the best anticoagulant therapy results. Inappropriate dose reductions are not associated with less bleeding. The bleeding is the same, but the stroke risk increases and the incidence of stroke increases. So you will not, by inappropriate dose reduction, protect your patient from bleeding, but you will expose your patient to increased risk of stroke.
Roman Jaeschke: So we should be using manufacturer recommendations.
Tatjana Potpara: Recommended, yes. It’s strongly recommended to follow dose reduction rules that are provided in each drug’s SMPC.
Roman Jaeschke: Now, I’m old enough to remember the time when we were using nothing to prevent stroke. And then for a decade or longer, we were using aspirin. And there are number of RCTs and meta-analyses showing that it is effective. And then came anticoagulants, which were much better, and we abandoned aspirin. Is aspirin an option? I could think about two situations: one, where there are really contraindications, and two, when it’s too expensive or inaccessible – in some countries or to some people.
Tatjana Potpara: Yes. It is tempting, but if you look back into [the] history of stroke prevention in patients with atrial fibrillation and you look closer into trials testing aspirin and there are meta-analyses, you will see that all trials but one – [the] SPAF trials – showed no significant relationship of aspirin with stroke rate reduction. It was only one trial – and all subsequent meta-analyses’ findings are mostly driven by the results of [the] SPAF trial, a single trial. So overall, there is a modest, statistically insignificant impact of using aspirin in terms of stroke reduction. If you look closer into meta-analyses and if you exclude [the] SPAF trial, then there is no significant relationship with stroke reduction. Another important aspect is that in the current era of NOACs and improved management of vitamin K antagonists – in comparison to 20 years ago – bleeding rates are quite comparable if you look at aspirin or anticoagulant therapy, especially NOACs. And we do have various trials to show that. So given the problematic questionable, if any, efficacy of aspirin, and considerable bleeding risk, giving aspirin to a high bleeding risk patient is not an option. If there is a true contraindication to all anticoagulant therapy, then we should look for alternative treatment, such as left atrial appendage occlusion. But aspirin is not [].
Roman Jaeschke: Well, that answers the question fairly clearly. Another medication, another question. In some circumstances we see people being put on proton pump inhibitors to decrease the risks of bleeding in anticoagulated patients for a variety of reasons – here for atrial fibrillation. What’s your pattern of practice? What’s your opinion about PPIs in anticoagulated patients?
Tatjana Potpara: Great question, thank you. There is no evidence to support routine use of PPIs along with NOAC therapy, of course, but if there is a combined antithrombotic therapy or specific pathology suggesting that protection would make the difference, then of course in combination of all anticoagulants with other anti-platelet drugs, it is important to also include PPIs to reduce the risk of GI bleeding. Or if there is a known, diagnosed GI pathology that should call for using PPIs. But there is no evidence to support routine use in all patients receiving [] therapy.
Roman Jaeschke: OK. Now we have two more questions here. One is fairly specific, which is the use… maybe I will read it. What is your opinion on using ticagrelor as part of the triple antithrombotic therapy in patients with atrial fibrillation during hospitalization after PCI, after percutaneous coronary intervention?
Tatjana Potpara: It’s a challenging situation because in such patients, having atrial fibrillation and having acute coronary syndrome, we have to balance 3 groups of risks. There is ischemic vascular risk of no coronary event; there is a risk of cardioembolic stroke; and there is a risk of bleeding, which is already increased by combining anti-platelet and anticoagulant drugs. Anti-platelet drugs will not protect from stroke. Anticoagulant therapy will not protect from stent thrombosis. So we must combine them, at least early in the course of acute coronary syndrome, and early after PCI. And in the modern era, there are lots of options to personalize the treatment of specific patients, taking into consideration the individual patient’s ischemic risk, thromboembolic risk, and bleeding risk. So why is ticagrelor not routinely recommended? Because we do not have sufficient data to support its use. There is a small proportion of patients with AF who have been treated with triple therapy including ticagrelor in the RE-DUAL PCI trial. But it’s just a hypothesis generating explorative data, insufficient to support stroke recommendation. In clinical practice, if you have a patient with specifically high ischemic risk and relatively low or acceptable bleeding risk, of course you can use ticagrelor, especially during hospitalization, but every caution must be taken not to take such therapy for too long. It’s just as short as possible, if needed.
Roman Jaeschke: Well, thank you. That probably answers the question fully. The last question I have here deals with pharmacological cardioversion. You mentioned that obviously that’s an option other than electrical cardioversion. And there are different options for existing cardiovascular pathology, or not. What is your preferred treatment? What is the specific treatment you could suggest for people to use, remembering that we are talking about global applications for both high-resource and low-resource countries.
Tatjana Potpara: The shortest possible answer would be to go for class 1C, propafenone or flecainide in patients with recent onset AF and structurally normal hearts, whereas parenteral amiodarone remains the only option for those with reduced left ventricular ejection fraction. Where available, vernakalant has been shown to be associated with the fastest cardioversion – the shortest time from administration to the restoration of sinus rhythm – but vernakalant is not available Europe-wide, it’s only available in selected countries. So the choice goes down to class 1C, propafenone, or flecainide and amiodarone.
Roman Jaeschke: Would that be attempted in a hospital with propafenone and flecainide or could you mention the doses which you use?
Tatjana Potpara: Well, the doses depend, there is a detailed guidance in the ESE 2020 guidelines for diagnostics and management of atrial fibrillation. And the doses depend partially on the patient’s body weight. But it’s not, if we are using parenteral drugs, then the patients must be within a healthcare facility and monitored for ECG changes and for heart rhythm. There is another approach, but it needs to be practiced carefully. And that is reserved for patients who [have] already tried that. It’s called “pill in the pocket.” In relatively healthy, relatively young patients with frequent peroxisomal atrial fibrillation in whom propafenone or flecainide have been shown to be effective, such an approach – [where the] patient has the drugs at [his or her] disposal and can use a tablet or two once the AF has started – has been recommended, provided that such patient has previously received those medications within the healthcare facility. Not necessarily prolonged hospitalization, but in the setting where heart rhythm monitoring and ECG analysis is available.
Roman Jaeschke: Well, thank you very much. I hope I’m expressing the views of other viewers saying that I truly enjoyed your presentation. I learned quite a bit and I want to thank you for answering our question.
Tatjana Potpara: And it was my great pleasure and honor to participate in this meeting. Thank you very much.
Roman Jaeschke: Well, I hope to meet in Krakow one day. Thank you.
Tatjana Potpara: Thank you.
