9: Prof Gerhard Wess, on dilated cardiomyopathy in dogs

[MUSIC] >> Hi everyone, welcome to the animal heart beat. I'm Jose and Novo Matos and I'm here as usual with Kirin Borje. We are professional veterinary cardiologist and amateur podcasters. >> Very amateur podcasters. >> Very, very. We have a great episode today. As again, we have a very special guest. We have here today, we does Professor Gajad Ves. I'm sure that everyone listening to this episode will know Gajad. Gajad is a professor of veterinary cardiology at the University of Munich, Germany. And well, Gajad did two residences. First, when internal medicine residency in Zurich, and then he did a cardiology residency at UC Davis, California. So Gajad is a truly double-boarded specialist. Gajad has a very large research output as published in many, many areas. But with a special focus on dilated cardiomyopathy. And he has recently shared the first European Society of Veterinary Cardiology guidelines for screening DCM in double-mints. Welcome, Gajad. It's a pleasure to have you here. >> Thank you for the invitation. It's a pleasure to be here. >> I thought we could start talking about staging of dilated cardiomyopathy. We have recently written a nice review paper for a special edition at the Journal of Veterinary Cardiology, where you propose a staging system for dilated cardiomyopathy similar to the one published in the guideline for mitroviral disease. There might be a slightly difference on how you have classified stage B1 and B2 in comparison with mitroviral disease. Would you like to guide us through that staging system? How would you define stage B in a DCM dog? >> Sure. Stage B is an asymptomatic stage in mitroviral disease, as we all know. And when I was writing my papers, I was always coming to that conclusion what to do with syncopy. Because syncopy obviously is a symptom that the owner can recognize. And then we said, yeah, in the occult phase, you can have syncopy, which doesn't make sense. So that would be also included in stage B, because the definition that I would propose is in stage B is no signs of congestive heart failure. And therefore syncopy would be allowed in stage B. And then the differentiation between B1 and B2 would be that B1 are the dogs with arrhythmias. And without echocardiographic detectable changes. So a boxer with VPCs, a doberman with VPCs or an Irish wolf hunt with atrial fibrillation. So we can put them into stage B1 and then everybody knows, okay, this is a dog that has only arrhythmias. And then in stage B, they have echocardiographically detectable changes. >> So that would potentially mean that a dog in stage B could still experience senden caractes? >> Or for sure. I mean, we know that from many studies, from play covered, from Michael Grady, these two great doberman researchers, and they always said, well, a doberman in the occult phase can die suddenly. This is our major problem, because the owner doesn't know that the dog is affected unless they come for screening, but the dog drops dead. I think there's huge challenges in this early phase in deleter cardiomyopathy, because my choice of health disease is easy, isn't it? Stage B, they have a murmur. The dog saying, hi, I've got heart disease, please investigate me. Whereas with deleter cardiomyopathy, there are no outward signs. Many of them don't have a murmur. And therefore, who do we screen? Who's most at risk? How do we look for that disease? That may be a ridiculously broad question to ask, but that's something that I find really challenging to answer when people ask me that question. What's your opinion, Goud? Do you stratify risk based on breed based on age? How do you look at that? >> Absolutely. I think this is why we also have stage A. Stage A are the breeds that raise the awareness for general practitioners, for owners, for breeders. Hey, here are breeds that have a high risk to develop the disease. The classical examples would be doba man's boxers, Irish wolf hounds, great dames, maybe Newfoundlands, San Bernard. So all these large breed dogs, when we say in mytovaf, we have the small breed dogs. Here we are talking about the large breed dogs that have this high risk to develop the disease. And then by educating owners and also breeders and veterinarians, we can remote screening exams. And in certain breeds where we have a prevalence of 30% or over 50% that absolutely makes sense. >> Right. >> I can tell you one story about screening. When I came here in 2003, wow, that's already 23, 20 years ago. >> Congratulations. >> Congratulations. >> Yeah, I was a young researcher. And so you started the university and you have to pick a research topic. So I thought, okay, doba man's, when I was young we had doba man's and I worked with clay culverts. So it was kind of clear, okay, it would be a topic that I was interested in. And then how do you start research? Well, you call up the breeding association. And they said doba man's and DCM, we don't have a problem with that. The German doba man, they are healthy. And then you say, okay, but you don't give up at that time we had already internet. So you go to the internet and start to search in the forums and then you search and there was no news about DCM in Germany. But then you can see, Arco, my friends, I have to tell you, Arco yesterday went over the rainbow bridge. You just dropped dead playing on the grass. And it was probably one of these deadly snake bites. And that raised my attention because there was a perfect research topic because we don't have deadly snakes in Germany. So either I find this doba man viper that nobody has ever detected or the disease detected is there. And actually that was the case. And then after many, many years, the German breeders, breeding association, they finally agreed on doing some screening exams. But they did that by themselves unorganized without the help of any cardiologists. They just had cardiologists doing the exams and then they came up with prevalence of 3%. And then they said, you see, we don't have DCM in Germany. Yeah, but then we looked at that and they only performed screening exams in very young dogs in one or two years old, right, which is way too early to detect the disease. And that is when we came up with our data and the different age groups just to show them, where does it make sense to screen and how high the prevalence is and we came up with the prevalence in Germany or around here in central Europe of about 58%. That's wildly high, isn't it compared to the background data that was provided previously. Yeah. But that's a good, a good starting point, Gahad. That's great. Just to remind our listeners. So as we discussed with HCM, cardiomyopathies in general have an age dependent penetrance. So it's more likely for the individual to develop the phenotype as they get older. So Gahad, if you would ask you a cat of age and age where you would say you should start screening your dobes, what would that age be? I would suggest to start with three years. And then what is very, very important, but you all guys know that is to repeat that exam. Some breeders are just coming to get that stamp yes approved by LMU. My dog is healthy. No, it's not. I would wish we have breeding certificates that is like a Snapchat. It disappears after one year from the internet. That would be great. But the good breeders and there are a lot of good breeders, they come yearly. And if there are financial concerns, I would suggest that if a dog is in the breeding program that you do yearly exams, especially the males because of the high potential to spread the disease and the female dogs at least every second year. If you, if money would not matter that much, yearly exams that would be perfect. It would be great to do it with engagement with annual examination. It's something that I think we face certainly in the UK and I'm sure people all over the world face these difficulties. So obviously this screening in youth for congenital heart diseases is fine. But as soon as we start thinking about any of the common diseases, very, very widespread acquired diseases, it's a massive problem. And I think this is one of the reasons people are super interested in genetics. Eventually that could provide a test that stratified risk somehow in youth, but we all know it's not that simple. What are your thoughts on the current status of genetic understanding of DCM? Is there an opportunity for using genetics to screen or is this something that actually at the moment we don't know enough about? We had performed a full genome study a couple of years ago and found something on chromosome 5. But that only means you find the highway. The next step is to find which parking spot did I lose my key. So right now we knew the highway and now recently it's not yet published but it's very late in the process. We did an even bigger study, again a multi-center study and we had some great geneticists involved. And that actually confirmed that we have something on chromosome 5. Interestingly it appears also that this is also a new mutation that in some humans can occur and they didn't know yet. So then on the next step we tested some human patients. And they seem also to benefit from the research. And that will come out in the near future hopefully in a human journal. From our side what we can say is it's not easy. We probably can explain the DCM phenotype. So where you have the echocardiographic changes. The arrhythmias we cannot explain that good. So it will be not easy that there will be a genetic test and it's working. And so therefore the screening will remain for a long time until we find a solution for that. But it's super difficult to find that correct genetic mutation. That sounds very cool. Just to stress to our listeners. So you have shown so there's a genetic test available for dobes. The BDK4 gene mutation. Can you explain a bit your date on that because you have shown that there are probably some geographical differences potentially between dobes affected by that mutation. Is that right? So is there a different genetic group between Europe and the US or not really? We did not look at the geographic differences. We just have double men coming from Europe, not only from Germany but from the countries around. And what I can say is in the first full genome study, we found only a signal on chromosome five and nothing on chromosome four where the BDK4 is located. We tested our population on the BDK4 and it did not mean anything. And also in the latest research that we did, there was again no signal on chromosome 14. I cannot comment on the American population. Maybe it's working there. Maybe it's not working. But in central Europe, unfortunately, I know that it is not working. It certainly wouldn't be surprising for there to be differences in different populations. Would it based on what we know about humans but also about boxed dogs and strata and the data from the US on strata in suggesting it's causative and then the data from the UK and Europe suggesting that it might be co-inherited at best with a causative mutation rather than being causative itself. It's so nuanced and complex. If we understood the factors that switch on the disease, maybe that's more important and understanding the genetics itself. Because if these causative, these trigger factors that might switch the genes on are easier to understand, then maybe we don't need to understand the genetic basis. Do we know of any environmental factors that are associated with deleticardomylathy and dogs? Is that something we should be looking for or thinking about rather than doing this complicated safari for genes that we may never understand? Very difficult topic. So far we didn't, at least my group, we did not find any trigger. But then on the other side we found auto antibodies against some receptors which we can treat with upto mayors. And then they had a much longer survival time. And so you don't know which came first. Was it a genetic defect and then maybe these auto antibodies came there. Maybe there is an immune component to the disease. And I was thinking maybe that's the case. So, but it's for sure it's genetics because otherwise you don't get a prevalence of 50%. And why do you only get it in in double months with 50% and in other large breed dogs, they don't have that. They also should have these environmental influence. So. I'm sure there are some cool factors and we just don't know exactly which ones are there. So, thinking about non genetic factors that some data support being associated with DCM. I'm thinking about nutrition. And it's a reasonably hot topic at the moment, certainly from the US that there may be an association between high legume diets or grain free diets and the development of a deletic cardinopathy phenotype. So, my personal experience of this is I almost find it impossible to buy dog food for my own dog in the UK that's not grain free. Most of the dogs that I see in this country are on, you know, 50% and 60% are on grain free diets. I've never seen a case that I believe is nutritionally associated cardinopathy. What's your experience, Goudon? What are your thoughts based on the data that's out there? All right. I mean, we all agree that coca-cospanials have torrent deficiencies. And we all have seen that. And there I think is no doubt they get the torrent deficiency, despite the fact that it's in the literature torrent plus carnitine deficiency because at that time it was on vogue to give carnitine at the same time, but all our coca-cospanials get better on torrent supplementations alone. If we prove they have a torrent deficiency. Cocospanial is not a large breed dog, so they are special. Anyways, concerning the dietary-induced cardiomyopathy, we have seen some cases also in dog commands. In Germany, it's not that high the amount of food that not 50% of the dog foods are grain free, but a lot of people are feeding grain free. When we diagnose DCM, we always talk to the owners. We already talk before with them about food. And my team is very eager to ask all that thing. And then sometimes I say, it's a mitral valve dog. You don't need to talk so much about grain flavoured diet. But because they are trained to talk so much about diets, we do that. And actually, we started, if we study in our dog moment population, because we wanted to see if there is an influence on it. The problem is, in the moment, when you talk about, we are performing a study on dog moments, on grain free diets. And potentially, there is an influencing factor. Now most of the dog moments that come to us, they are already switched because of internet. They read about the study. And then the community among these doberman owners, they are so highly connected. And then they say, "Hah, they think there might be a connection." So I just switched my diet. So all these follow-up studies, we could not do anymore because we wanted them to change the dogs to a normal diet, but the owners already changed them. But we sometimes see is also in the doberman some torrent deficiency, but not very common. That would be really rare. In other breeds, we diagnose torrent deficiency even when dogs that were barfed. Right, okay. Which, where you think, wow, that's strange. If the one you've got is torrent, right? Yeah. But it seems to be the combination of whatever they give and certain kind of meats. We had also, like in the literature, some dogs that were on grain-free diets and they became better after we changed the diet. I would not say it's a huge amount, but usually when we diagnose DCM, we try to search for an underlying cause. Is it tecicardia induced cardiomyopathy? Especially if you have a breed that does not fit. Like you have a young lab or he shows up as on echo at DCM phenotype. And then, okay, he has a superventricular tecicardia. And often I think people would guess, yeah, the superventricular tecicardia secondary to the DCM, but it's actually that they have reentry tecicardia. And that was actually the cause. How do I know? Because we treated it and it was really. reversible. And many of us have seen those cases. So we are searching for techie-cardia and use cardiomyopathy. We are searching for especially food influencers. And then we measure torrent usually. And we try to change the diet anyways to a normal commercial diet. So would you hold every dog that you diagnose with DCM irrespective of breed? Not necessarily especially the breeds where you don't expect it. If it's a street dog, not a pure bread dog that shows up with DCM phenotype, then I would do that. Or if they are especially young or yeah. And then the other breeds, I think it is not a bad idea to hold to them if it's financially doable. A great day and can have VPC, to unboxer all these other breeds. And often you don't see them during the echo or during a short term ECG. Yeah. Just regarding phenocopies because as we were saying, Gahad, there are a couple of DCM mimickers, diseases that may mimic DCM that are not familiar or genetic. And you already mentioned some of those. You published some interesting work on hypothyroidism on dobes. And so as pretty much every listener will know, hypothyroidism may potentially cause left interagrecystolic dysfunction and maybe a mimic of DCM. What is cool about dobermans is they have a high prevalence of both DCM and hypothyroidism. And you have looked into that. Can you just summarize your findings to us, please? Yeah, as you said, we had, for example, the reason why we did that study was dobermans are sometimes diagnosed with both with DCM and hypothyroidism, which sometimes I think is a challenge. How to test that a dog that has an advanced DCM that they have not you thyroid six syndrome. Just measuring T4 might be a problem. But for that study, we did a lot of of thyroid tests. So we were sure that those dogs that we diagnosed actually had hypothyroidism and the prevalence was actually quite high. Some of them also had DCM. And the reason why we had started that study was that often we got cases back. We diagnosed DCM and then the home that maybe later made a test for hypothyroidism. And then they stopped the cardiac medication because the implementation was, yeah, it's just hypothyroidism induced or mimicking DCM. So I wanted to see if that is real or not. And the outcome was actually they're unrelated. So a hypothyroid dog, if you treat them and you manage them, you would think the DCM is reversible. But it was not. It was actually progressing to VPCs progress to the heart get larger. You could again speculate about an immune component. Maybe hypothyroidism is has a immune component to it. And maybe the DCM with our auto antibodies, for example, also. So maybe they have something on a gene in common that manipulates the immune system so that they have a, again, a trigger to develop either the DCM or the hypothyroidism. I don't know. This is pure speculation. But it's interesting idea. But that's cool. But that's so you showed that hypothyroidism is not the theology, the cause of DCM and doesn't affect progression. Would you in your clinical practice, would you still measure T4 and TSI in a doby that has a DCM phenotype or NECO? Or would you only do that if they have clinical signs suggestive of hypothyroidities? We only do that when they have clinical signs. Kirin start talking about halters and we would like to have your input in a couple of things. DCM in doby's may have two different components. An electrical de-arrangement where you only have a retmiase or a morphological de-arrangement where you have a dilated hypo contractile ventricle or you can have both. And so halters are really important as everyone knows to diagnose the electrical component if you want. So on your guidelines, the European Society for Veterinary Cardiology guidelines, he described the cat-tops very neatly. Do you think it plays a role? Or would you do a 24 hours or 48 hours holder? Do you think it does play a role to do a longer holder to detect ventricle ritmasing dogs? Do you have any data on that or what are your thoughts? Do 24 or do you do 48 hours? We do at the moment still 24 hours. There was a recent paper that showed that if you do it longer, 48 or 72 hours, of course, you have a higher chance to detect some arrhythmia and there is a day-to-day variability. I think it also has to be manageable. We see every week like 10 dobermins and we have to analyze all these holders and we have to have the devices back. So just practically, we stick at the moment with 24 hours. And probably the number of EPCs or the malignancy of that that you detect only on a 48 hour ECG is probably not that dangerous because if they have a lot of access and if they are dangerous, you usually see them on 24 hours. I tend to run 36 hours just because I'm annoying and I exclude the trip to the vet. I'll take out the trip to the vet in the journey home when I'm looking at AF heart rate, for example, or I want to interpret were those one on two VPCs that I saw or when the dog was very stressed on the echo table were they important when the dogs at home. I would say that having looked at that data quite a lot, I've not analyzed it, but just my impression is that the worst day with me is are in that first 12 hours because of the catacoleumine effect. I don't think that would lead to overdignosis because I think a substrate fear with me is the GCM, it's the disease. But I think when the trigger, the catacoleumine is there, that brings it out and helps to help you to see it. So from my point of view, I would imagine that 48 hour halters probably not going to help any more than 24 hour halter, but it's interesting to see how different people work and what their thoughts are. Big of a thing is we don't really know data, data variability of VPCs in in dobermans, I think, I don't know if you have any data on that. So we are still we still use the data from boxers and the human data on 85% variability or something like that. That's right. Do you think, do you think dobys might be different or do you have a feeling that the data variability might be similar? We looked at those data, but unfortunately I don't have them present at the moment. But yes, we looked at the data, the variability, it's there, especially in the low numbers. Because I mean, that's kind of clear that if you have a difference between 150, this is a huge difference, but clinically it's not. And the same is, does it matter if you have 2000 or 4000 VPCs, it does not. It's a statistical difference, isn't it? Not that clear. Your question probably goes towards treatment later. How do we judge if we were successful and we are not looking at numbers. We are looking at malignancy criteria that predicts certain cardiac death. Yeah. Honestly, we should stop talking already about it because we want to talk to you a lot about echo, but that's the hot topic. Let's talk about standard cardiac death. That's that's the big thing. That's the big thing, isn't it? And then we just is itching to talk about exactly that. Exactly. Exactly. If that's all right with you guys. So we have, you have this very cool study with very cool stats on predicting sudden cardiac deaths in in dormant and then we are talking about holders. If I remember right, the total number of VPCs, you know, play a role. It was not a risk factor for sudden cardiac death was malignancy. How fast the VPCs were and so on. But I still wanted to ask you that does number matters or not at all, 3000 or 8000 VPCs? That's correct. Why should 2000 slow VPCs? Be more malignant or having a higher risk to die suddenly compared to 100 very fast ones. I mean, where you have the danger of R on T phenomenon. And that study actually showed it from all these studies that we did this, I think, is one of the coolest because in that study, we compared dogs with DCM to dogs with DCM. Some of them survived one year and the other ones died within three months after the last exam. And we hold the all our dogs and in our double man study ongoing now since almost 20 years. They come yearly back and They get very special rates so they are coming back because it's very cheap. So we have a lot of data. Then as you think in some breeds it says, yeah, we start treatment with more than 1000 VPCs in boxers. Where is that number coming from? Somebody thought 1000, yeah, let's take 1000. So choose a number, right? Yeah. It's just a random number. And if you would ask somebody, what is the most dangerous thing in a dog woman? You have two dog women. Like today is Tuesday. Today we have like five dog women's downstairs. When is the day? Can you tell us about the D day? I heard about the famous D day in the day. The D day. Well, the famous D day is Tuesdays and Fridays. They are coming on. I'm so sorry. We are taking away from the dog. We're taking away from the dog. The irony. The irony. All right. So they are coming on Tuesdays and Fridays and because they are a lot of work, then we call them maybe the D day. So today is D day and there are five dog women's downstairs. Two of them are maybe diagnosed with DCM. And then one might die in the next few weeks. And we were always wondering how can we predict the risk to die suddenly? If you think about it, if you compare dogs that die suddenly as it is done in most studies to a healthy control population of healthy dog women's, statistically everything will come up that defines the disease. Sure. So that is that was not the cool thing. So we select the dogs that died within three months and compared them to the women's with DCM diagnosis that survived at least one year on follow up. And then this special software statistical tests generated thousands of decision trees. And the thing that was always, always and all these trees came up on top was actually cardiac size. And it was left ventricular and diastolic volume, but that is only a representative of the DCM phenotype. We tried separately, can you use end systolic volume or ejection fraction or anti-probe NP as a predictor of a cardiographic changes. All of them you could not analyze separately because they go parallel. A dog that has a typical phenotype DCM, a big heart with a poor contractility. That is the major risk factor. And the software then calculated cutoff values for the obamins and basically it found if the heart is normal sized, the only predictor of sudden cardiac test was if they had V-tex. If the heart was enlarged, then the next decision trigger was the B2B frequency, the V-max. We enter 26 different halter criteria into that. The amount of couplets, triplets, whatever, 26 halter criteria. And we gave them all the echo data and biomarkers and then it was calculating. So basically the second most important thing if the heart is enlarged was the B2B frequency of the fastest VPC. If that was more than 260, these dogs had a very high risk to die suddenly. So there we have this magic number and it actually changed also a little bit the way how I'm looking now at our door moments. They are all in prospective studies. So I'm not changing them now and change the classification because they are still in the study. But already at the beginning it was kind of the correct criteria how we categorize malignant or sometimes we call it B9 arrhythmias. They are not B9 but they are not as malignant as the other ones. Then sometimes when we are on the borderline, I'm always asking so how big is the heart, how is the contractility. If the heart is still normal, I'm not so pushy anymore to treat them with anti-arhythmiics. Versus the heart has the DCM phenotype, it's pretty big and they have fast VPCs, they have to be treated otherwise they die. That's really interesting because I think instinctively we all look at halter criteria and say, oh well, this dogs higher risk because the arrhythmias looks like this, we should be contextualizing that in the echo findings and how marked the changes are on the echo. I guess that reflects the severity or the, I guess that reflects the substrate and the arrhythmias, the trigger maybe or the combination is important. Gerhard, you have a crazy amount of data out there on echo diagnosis of DCM and so on and of course, echo is a gold standard and that's how we're going to diagnose the disease. Volumes versus linear measurements. Would you still measure the left ventricle with a simple linear dimension or would you just really rely on volumes? There are two different things, do we still measure yes? We still measure M mode. And we are also looking at the diameter. There is one very, very important thing that is sometimes forgotten because there's a welsh of data on normalized values and for my to love, everybody uses either the Cornell or the ester data to normalize LVIDN. In doberman's this is not working. In doberman's we have much better breed specific data and I just like this morning I had a dog where LVIDN was normal but actually the dog had DCM because he was above the even the M mode cutoff values and also on simps and so don't use LVIDN in a doberman, use the breed specific reference values and that accounts for all breeds basically. I was going to say I think that's true across all breeds because my trovar disease is so prevalent and the epic criteria are so well known and well discussed that of course people, a lot of practitioners revert to these normalized dimensions because that's the default in my trovar disease. I couldn't agree more. I think these breed ranges are super important for springer spaniels, for coca spaniels, for the site hounds, I mean they're so different to one another, they just don't fall into that normalized Cornell formulae. Yeah, so coming back to your question, yes we still measure it, we still look at it but I trust the simps and measurements, we measure them from the right side, from the left side and then we take basically the larger one because you cannot overestimate but you can underestimate by bad echo views basically. So then take the larger one and in one of these studies we have shown that it's more sensitive but yet very specific to use the simpson and we proved that in longitudinal studies. I gave a presentation a couple of years ago at ECVM or ACVM and the speaker after me was a professor from the Mayo Clinic, their leaders in echo and he was following our discussion. And he said he's surprised about this discussion M mode or volume measurements because in his lab he let the measure M mode and volume so at the end his residents have to delete the M mode. You could do it. No, no, it's still good to do M mode but if you do M mode I would highly, highly recommend to measure also EPSS because this is the way how it changes my exam. This is such a quick test when I'm in the plux you, porous donor long axis view from the right side and then let's say I make a quick M mode through the long axis and then just move the cursor and do EPSS either there or in the short axis and but I usually start in the long axis and then when I see EPSS is small I know this will be in a relaxed exam. If I can just eyeball EPSS looks a little bit large or even it measures large then I know okay that will be now more work because I need perfect views from the right side, perfect views from the left side for two three chamber views. We probably will measure strain we do diastolic parameters and so on because this dog has most likely the DCM phenotype. So just this quick simple and very old parameter EPSS is super and it was actually better than just M mode. That's great to stratify your risk. Yeah. So it has been shown that internal diameters are different, are not between short axis and long axis the measurements are not interchangeable. Is EPSS interchangeable? Do you use long axis for chamber, five chamber and short axis interchangeably or is there a difference on EPSS also between short and long axis? Well now we come to an interesting question. It has been shown there is a difference between long axis and short axis but then you have to ask yourself why is there a difference? If you use a 3D probe in the long axis and you do it hard way, in the courses I always talk about easy way and hard way, hard way means you go one, rip spot more cranial and you look backwards and you go away from the sternum and scan more from inside of the thorax and look backwards. Then the heart also looks a little bit different. It is oval and it has not this bullet shape versus you do the easy way, you scan straight up and then the heart looks like a bullet. So if you do the hard way and then you do, you use your explain view on the 3D probe. The measurements are exactly the same. Why are they often larger in the short axis? Because probably we are scanning a little bit oblique. While you turn the probe, you manipulate it too much so that you cannot see is the heart maybe too steep and then your measurement would be wrong in the short axis versus the advantage in the long axis is you can see if you are scanning oblique or not and in the short axis you cannot unless you have a biplane view. So that as a comment is there actually a difference between the short axis and the long axis in the internal diameter and about the EPSS? I would say not. I also would not think that there is a big difference there. Most of the times I do it in the long axis but I also do it in the short axis, the EPSS and it should work. Regarding normalizing volumes to body weight. So initially you and others have used body surface area to normalize the volume. And most recently you have shown that you can also normalize it to body weight, which one is better or can you use them interchangeably? Excellent question. So in the very first studies that we did about the Simpson method, we normalized them to everything like body weight to power of 1/3 but that is used for M mode. And then to kilogram and to body surface area. In the very first study that included only 300 dogs at that time, we found that body surface area and kilogram they were very similar. But because in humans they use body surface area to normalize we thought, OK, we just do that as well. And for dog remains I still like that because we have so many data that I have no reason to change it to kilogram. But then when we recently published this normalized a long metric study with 1200 dogs, then we found that the theoretically correct normalization by kilogram is also the best that we used in this huge amount of data in different breeds. And also in that paper we provide the cutoff value of like if you have LVID normalized to kilogram, then you have one cutoff value. And it's a quick thing because probably you also have it programmed into your machine. But if it's borderline, I still prefer the table because the table is based on a special statistics where you don't have just a normal logarithmic line. We actually had these upper and lower normal values kind of were adapting like a curvilinear adoption to the data. And therefore the table in that paper is actually better than just to normalize it by kilogram if you have an average breed dog. That works pretty nicely. I still look in my machine when I do the quick thing, we have the normalization to body surface area for the breed specific ones. And also the kilograms in doberman, boxers, saluki, and so on. We only use the body surface because we have data. In the other ones, if it's a mixed breed dog, I look at the normalization by kilogram as a rough thing. And if it's borderline, I take out the table and look at the table because the table is more precise. I mean, the very advanced one you can diagnose with any diameter. You even can use friction and shortening for that. Even fractional shortening. But I'm just kidding about fractional shortening all the time. Because fractional shortening, when I started here, I got a couple of taxhounds referred for DCM, second opinion based on fractional shortening. And I mean, a taxhound doesn't get DCM. And this was just a wrong measurement. If it's measured correctly, then the parameter is probably OK. But I'm just always trying to teach, don't refer on one single parameter in the special effectional shortening without end-diastolic and end-sustolic enlargement cannot be correct a low-fraction of shortening. It's called if that's related for a reason. Yes. Well, there are a systolic. Do his functions as well. And for example, we were talking about strain. If I have an end-sustolic diameter enlargement, I always measure strain. And I want to confirm what we see. Or if we have regional hypokinesis, we want to confirm that, we always measure strain. So we talked about linear dimensions a little bit. And we talked about normalizing for body surface area, body weight. I have two questions actually about echo. One is slightly more advanced in inverted commas measures, like specle tracking based techniques. So thinking about strain, strain rate. Is that something that you would use routinely, either, as part of your screening protocol, and if so, how? And the second part of that is, would you use it in cases that have got overt DCM? Do you think those advanced techniques hold any value for prognostication or risk stratification? I think strain will stay. Strain rate may be not. Because strain rate, even with specle tracking, is still too noisy to reproducibility in my-- I'm glad you say that because I find it very noisy. Yeah. Strain is a quite robust method. And it's quite easy. You have a steep learning curve. I mean, the main goal would be to diagnose the DCs earlier, then right now. And we have several studies running. First step was to establish, again, using specle tracking methods, normal values. And a couple of studies already published. And there will be more coming out, also in the global longitudinal strain, using four to three chamber views, which is now kind of also in the guidelines of humans as an additional tool. And I think we will come there. It was a little bit the same with T-Shield or T-Shield velocity. If you think back 10, 15 years ago, it was still quite new. And only in high-end machines, now it's included in every machine. Everybody's a god. I haven't any here. Yeah. And in certain DCs, it's very useful. And it will be the same with strain. This is what I'm predicting. Because this is a standard parameter now. In humans, we still need a few more data because we have done strain evaluation using the color T-Shield Doppler technique quite some years ago. There was too much overlap between the groups. But that might have been because of technical issues that we made segmental analysis, like base, mid-APEX. And then you had so many individual numbers. And they were not so good reproducible. Now, with these methods, if you give these loops to some people and they just follow their instructions, it's very good to reproduce. And we are getting probably more and more in the future, these artificial intelligence and AI analysis, automatically analysis, in the future. And then it will be included. I'm very sure about that. But I cannot say that I use it on a daily base in screening. Because now we know the normal values, but I don't know which value would put that dog into a risk. This is the next step. We will do that. We are currently doing that. But I cannot give you a number yet. There are software differences between different vendors. And they are working on that. That if you measure it with a GE machine, that you get the same results with a Phillips machine, or a TomTech, or Siemens, or whatever, they formed groups. And they are getting better. to harmonize, but probably is also for the individual patient. I think there is a big thing that if you start with a dog, a man screening, you have its baseline. And then the dog comes back and then you can compare again, how is the strain now? I think this will be an interesting part. As we do with our hard size, I always ask or look up how big was the hard last time in diastole, in cystoly. And how is it this time? Oh, it's still normal, but it gets bigger. Okay, we have to look at this dog a little bit closer. Yeah, I think that change and the rate of change is important, isn't it? In most of the diseases we see, but I think it's underrepresented in the literature, maybe. And I think the rate of change is not something that many practitioners think about. They think about the diagnosis on the echo when they might see a case, but I think actually a lot of the nuance in decision making for those long term cases comes from that serial echo and the change over time. And my second question actually is going back to linear dimensions. We've not mentioned left-haterial size. And when we've talked about, when we talk about mitral valve disease and we talk about hypertrophic cardinal pathy, we focus a lot on left-haterial size because obviously it's a big part of risk stratification, the decision to intervene with treatment. Perhaps it's not such a big part of the related cardinal pathy. Our discussion hasn't gone there yet. And we treat with Pymabendum when we diagnose stage B with systolic dysfunction, chamber of delation, we're not thinking about adding Pymabendum only based on actual size as we would in mitral valve disease. Where does the assessment of left-haterial size come in for you? And does it influence your decision making in terms of treatment or discussions with owners of an sudden cardiac death or risk of heart failure? - We are looking at the left-haterial, but it will only dilate in late stage B2 because it would not like in mitral valve where we have the blood going back to the left-haterial, it will only dilate in the more advanced stage. And we would use it as an assessment of the development of congestive heart failure, so of stage C. And LA to AO in the short axis, but recently I love more and more just long axis normalized to kilogram to exponent. That is really good. - You mentioned left-haterial fraction of shorting, which is great that you stressed it 'cause it would be very important to the listeners. Something that I also always thought interesting was regarding LV injection fraction. That's a big one in human, isn't it, to define the disease and to define prognosis? They look a lot at LV injection fraction. And looking at your diet, the both end-diastolic volume, end-diastolic volume and then systolic volume are related to sudden cardiac death. So is it different? Do you also look at injection fraction in dogs? 'Cause looking at the stats, I would think injection fraction would be a big one, would be up there. Why is that not the case? - Oh, it is the case. - The injection fraction was in this sudden cardiac death paper. It was going parallel with LV, I lift it in particular, end-diastolic volume and systolic volume and injection fraction. In humans, injection fraction is actually number one detector or predictor of sudden cardiac death. And this is why we had included that in that study. But because they all three parameters. - A very correlated, right? - Yes, yes, yes, yes, yes, yes, yes, yes. So if I had to pick one, of course, okay, cool. - And your reason why we are not using it more is, I actually don't know because most of the studies started to generate just end-diastolic and systolic volumes, and not so much the injection fractions. And I still like to look at those two parameters separately to know is it more volume overloaded or is it more systolic dysfunction? The injection fraction correlates quite good and the cut of value would be probably around 40. - We have this tradition of talking about biomarkers. We need to talk about biomarkers in every single episode with mixed feelings. But you have published a lot on biomarkers and we have talked about screening and so on. Can you tell us when are biomarkers useful in screening? And what is the right biomarker for B1 versus B2? - I love biomarkers. I love biomarkers because they are good if you ask the right question. - Right. - And this is our job of the experts to educate our colleagues. What is the correct question? If your question is, does this dog have mitral valve disease? It's just use your stethoscope. This is the best biomarker. You don't need BNP. Every dog has a murmur that has mitral valve disease. On the other side, it's very useful in my opinion in diseases that are not so easily to detect clinically in phyloincardium myopathies and in dogs with cardiomyopathies. Where do I see a purpose? It's a good pre-screening test. So if you have dogs in their art countries where you travel three hours to the next cardiologist in Sweden, for example, and there is a doba man or another large-wig dog. And the owners here now, okay, I have a doba man, do I need to travel three hours? What you could do as a practitioner is to use, for example, anti-provenry, which will predict echocardiographic changes. So the phenotype DCM, or you pick troppoin and eye, which would be a slightly better for detecting arrhythmias. So in my opinion, anti-provenry, really good to predict cardiac enlargement. Troppoin and eye, a little bit better for arrhythmias. For the perfect screening test, in for stage B1, none of them works. Because there we have the arrhythmias. So there you probably cannot replace the holder by a biomarker. What you could do is you run quite long ECG in your practice if somebody is doing an echo, you have an ECG attached. And if you see one VPC in a doba man during your echo exam, that means the likelihood that this dog will have more than 124 hours is very high. On the other side, it's not very sensitive. So you can tell the owners, if you collect arguments, I think we need a holder in this dog because I saw now one or two VPCs and the likelihood is very high. In some countries, echo is very expensive. Then maybe a pre-screening test using one or both of these biomarkers would be good in my opinion. A flip it around. There are countries where a biomarker's super expensive. An echo at a general practice level is very accessible. You know, I remember years ago, I, I, I, I wanted to quantify this quite a long time ago. I presented in Russia and I did a whole lecture on biomarkers. And I'd suggested the title and they'd approved it. Fantastic. Did the talk. I was really happy with how everything went. At the end, somebody put a hand up and said, given what you've said, why wouldn't we just do an echo? And that's exactly what I'm saying. You know, echoes are probably kind of expensive and, you know, biomarkers would be cheaper and, and, you know, how many of you in this room are doing echoes? Everybody put their hand up, you know, 500, 800 people put a hand up. I said, well, it's very different to the UK. You know, and how expensive are biomarkers? Well, they were about five times the cost of an echo. And I did exactly the same thing a couple of years later in Brazil. So there are definitely countries where biomarkers are inaccessible. And echo is much more accessible. And for those guys, obviously, it's a no brain or echo is, is the way to go. Absolutely. And do I be a marker? Do I do them? Well, I don't need them. But there are some time. I mean, troponin, I is quite good marker. Sometimes it's already increased slightly. Yeah. While our echo and the whole to still normal. So we call that the last normal exam in one study. And so these dogs, because they're in our study, they would come already after six months back for the next exam, but they don't have to pay much. Anyway, so, and I completely agree. You'll have to keep the costs in mind of the biomarker. But maybe the cardiologist, there is no cardiologist in this area as a pre-screening test to collect arguments. This is a good thing to send them to the cardiologist and in some countries where echo is expensive. If echo is cheap, do the echo, of course. What you just mentioned is an area that I have a lot of interest on. And you have so to detect if we want stage a dogs just before all over the deleted cardiomyology, just before they didn't follow any signs of the deleted cardiomyology. Stage A plus. And you have this data, as you mentioned, that both BNP detect earlier disease than Econ holder, didn't it? And is this something you are still looking at, a marker that will detect disease before over DCM? We are looking at some in-house biomarkers that are cheap and that could be run by normal practitioners for the A+ stage genetic test that would be the thing. But the Protect Study, just for maybe the very few people that may not be aware of the Protect Study, the Protect Study was a randomized clinical trial that has shown that PMOBEND and given to dogs, the dobermans with a cool stage of DCM, giving PMOBEND would delay the occurrence of clinical science, congesive archfell or send-and-cardic test by 9 months. So the Protect criteria were linear measurements. They buy their criteria to start PMO on right-person or short-texts, even linear measurements. What are your criteria to start PMOBEND and on Adobe? Do you also use linear measurements? Or would you use volumes? We still use our volume data. And you have cutoff values. What is normal and what is abnormal? If you have 55 as a systolic parameter, for example, in Adobe Man, would I start PMOBEND and in a dog that has 56 milliliters per body surface area? Probably not. I would probably say, okay, we have a starting systolic dysfunction and maybe we make another exam in three months and take a look. And then if it's confirmed, then we start. I want to clear diagnosis. Not saying that 56 is not clear, but I mean, 1 milliliters, you can adjust by measurements. And since they are kind of correlated to linear measurements and volumes, I would also do the same with the linear measurements. Only if you have clear evidence that their systolic dysfunction, then I will start. I think we'd all be happy if we make a confident diagnosis of the later card in the PMOBEND in the asymptomatic phase. Is there a scenario where you would start treatment with some rass inhibitions? Some asymptomatic, such as binocular or spironylactone in the asymptomatic patient? Would you use it instead? I mean, the data on asymptomatic inhibitors, for example, in humans in DCM, they're not bad. And whereas I don't see any point in my drovath disease to give it in that phase in DCM, I see a point. And there's one retrospective study from Michael Grady with all that doubts a little bit because of retrospective nature. But at least this is better than nothing. And we have actually a prospective study on that topic also ongoing, which is to pull out the data and just see if it makes a difference. The study is already quite long ongoing to me studies, but big data probably. And then I can give you more evidence-based answer. But I see a potential for an asymptomatic phase in stage B2. And spironylactone at the moment is that something you consider using in the asymptomatic patient or in fact in the stage C patient? I mean, if you give the cardalys, for example, as a combi product, you get two drugs in one. If you want to give one, why not give two in one pill? Sure. That would make more sense to me. It was also a recent paper in double-man's in congestive heart failure and the outcome. I mean, the add-on of spironylactone was not that super convincing, but it would be included in our part in any way in congestive heart failure as a sequential nephron blockade. Yes. Where we start with thoracemyl, thoracemite, and then add maybe spironylactone and add later hydrochlorophyteside. How do you mention their humans and that ACNibuters are useful in humans? Something that is always very striking is beta blockers are very useful in humans and use as a first-line treatment in dilated caromyopathy. Why is that different in dogs? What's your thought about beta blockers on pre-clinical dilated caromyopathy? I start to cite humans. But humans are actually not a good model for us because most of the DCM comes from post-myocardial infertile. And this population is just different than the dogs that we see. And if you look at the data, most of the effect that beta blockers, ACNibuters, rosinibuters, and so on, is actually on lowering the blood pressure. High blood pressure in humans is the major one cause of having problems. And I think we all agree that in dogs it's not that big problem. I think the beta blockers in the later phase, Carvedolo, was very long hyped, also in veterinary medicine because of the Copernicus studies in others in humans, where they even gave beta blockers in heart failure. Initially, everybody was scared because if you give a beta blocker to a human in heart failure, you would think you reduced the contractility on the long term, it was actually better. And then I still remember when I was a resident in Marquitlson, was sitting with us in journal club and he put $50 on the table and said, if anybody can prove that a dog has an increased contractility on Carvedolo, here are the $50. And these $50 are probably still there on the table because we tried it. The value depreciating everything is improving. Many people tried Carvedolo and nobody can show that they have an increased contractility anymore. As an anti-aruthmic drug is not very good. We tried that also at the beginning. It was a little bit disappointing. So we stopped doing that. You just mentioned anti-arhythmics. So one million dollar question and I don't we have no diet out there, but still what's your first line in anti-arhythmic or ventricular arhythmic? Well, when would you start to treat ventricle arhythmics maybe first? Based on the malignancy criteria, which are my most important is to look for R&T and the VMAX, which are correlated. The VMAX, if the velocity is more than 250, 260, then we start treatment. And as we discussed before with the sudden cardiac death, a big heart triggers me much more. So the phenotype DCM to start and use anti-arhythmics. Because many private practitioners are listening to your podcasts, I think it's very important to mention also that there are a lot of VPCs that are slow. And we call them accelerated idiom and triglyrythm. So VPC with a rate between 60 and 16180, I just call them differently accelerated idiom and triglyrythm just to take away the burden from the shoulder that you need to treat that. Because if you say, okay, there are four in a row. How do you call four in a row? Well, this is a VTAC. But if it's slow, it's not a VTAC. A VTAC means yeah, I need to treat. But if you call it, yeah, there are four beats of accelerated idiom and triglyrythm, you don't need to treat them. So the speed or the beat-to-beat frequency of the VPCs, this is very important for me. The numbers of couplets, triplets or VTAC solvies on the holder, those would be all malignancy criteria. And then which drug would I use to use? I don't want to influence anybody here because again, we started 20 years ago. I was sitting there and then I was thinking how to make cool dopamine studies. And then I set up 19 years ago, maybe, different legs. Like where I said, this is a dog that has no echocardiographic enlargement. He has just arrhythmias. And then what kind of arrhythmias? Different legs, different studies, how they get prospectively randomized to get the drug. And the same then, if the heart is enlarged. Are they malignant? Are they kind of benign? Different treatment options. So I have maybe this 1 million question answer. But I need to do the analysis and I think now I see this. I was waiting. When the time it did drop it. So I mean in these legs, I can tell you what is in these legs. they cannot spoil which one is better because I don't know. Honestly, I don't know. - Watch this space. - Yeah. - I will come back to the podcast with Esther as well. - Oh yeah. - You know, we're thinking about doing a research podcast where we discuss with researchers at the website. - Absolutely. - So let's do it. Let's book you for that right now. - Yeah, that's great. - Everybody who likes that podcast, please don't forget to give a like. (laughing) Subscribe. - Subscribe. - Yeah. - Subscribe to the channel. - So that you will get the updates on that. So what do we do? (laughing) So what do we do? We have for the very malignant ones, we have either a meodaron versus Sotolol initially in combination with mexility or now in combination with flakyene. And then the other legs are Sotolol alone or some non-enter rhythmic drugs to see. Then we know which one is working. We had one thesis about that topic and the difference between amyodaron and Sotolol plus mex was not big. So it's not a clear winner. Otherwise, we would have already presented some data. This has been presented, but only as a doctoral thesis. And that was already 10 years ago. We all know, I mean, Clay Coverd always told me if a doberman has these malignant secretariat or if they have a syncopy, you need to treat them otherwise they drop dead. And he learned it hard because his own dog dropped dead. Many, many years ago. But we don't know which one is the best one. I think they are both very good. I'm just reluctant to say amyodaron is so good because many people listen to your podcasts. And amyodaron is a dangerous drug. It's a dirty drug, isn't it? It only I think we should teach about amyodaron as it is done in humans. It is the last drug that you use after you have used a bunch of others. Before you're in humans, before you implant a defibrillator. And I think if we can bring that message to all these veterinarians there because I have seen actually dogs on, I should not say that, but 30-degree AV block with a ventricular escape on amyodaron because somebody thought this needs to be treated. So I think we, as experts, need to be also careful to educate. This is a drug, it is potentially very good, but it also has bad side effects, liver enzyme elevations. We see frequently on long-term use on endobamans, sometimes not all of them, but sometimes we see that. This is probably the most side effect that we see in endobamans. It is an effective drug, but as you said, here in dirty or dangerous. So only use it if you may be consulted with the expert of your choice about arrhythmias. I think don't forget that. If you're trying and you have this really bad ECG, there are cardiologists where you usually refer the case to anyways and everybody will be happy to help out and say, this one I would not try first something else. Pick up the phone. That's an incredibly positive message to end on. - Okay, just the two final, can I ask you two cheeky final questions? One, Gahadis, such a law, how worried, nervous are you to giving Sotalol to a dog with systolic dysfunction? We discussed that a lot. Okay, there is systolic dysfunction, of course, Sotalol, SMB2 blockery effect. Are you worried? Do you have seen dogs that you start Sotalol and you and then they decompensate? What are your thoughts on that? - We are always routinely titrating up Sotalol everything within O'L. At the end. And sometimes you have to make the individual call that this dog had a V-TAC with more than 300. So he's a high risk patient. So you probably don't want to titrate it up over one month, giving you a starting with the court of those in the next week half. Here I would go in faster and I would then, for this period, double the p-mobendant to counteract that negative inotropic effect of Sotalol or whatever other drugs you use. But I am not super worried to use it in DCM, even at once cases. - Sometimes there is this concern that dobes may be more sensitive to a meodaron and may have more adverse effects. Do you see that or not really? - I mean, do women have, per se, more liver problems? I mean, have a high prevalence of liver problems, independent from the heart. And maybe they have more problems, but maybe it's only because this is the breed where we use it most commonly. But we also use it in other dogs. One thing maybe we have seen German chapards with probably inherited ventricular arrhythmias and they have been on previously. They came with us on Sotalol and I think one message is for me that Sotalol as a single drug in German chapards is probably not super good because it has been shown by Anna Kielso that it might be pro-arithmetic and actually in that dog. We took it off and then they were much less. But the dog still had malignant ventricular arrhythmias and here we use an amiodaron as an example. The numbers of dogs on amiodaron are not so high in other breeds where we can say they don't get liver problems. - Brilliant. - So what we tend to do at the end of our podcast is to ask our esteemed guests for their top three take home messages for the listeners. So I don't know if you can distill the last hours conversation into your top three practical points for people. - Okay, my top three take home messages is talk to your clients about their breeds inform them about the disease. Oh, you have a dog woman. Do you know the disease exists and tell them inform them? Then top two biomarkers can help for pre-screening. So and then concerning echo methods we talked so many about volumes. Of course, I love volumes and advanced measurements. For sudden cardiac death, it's not the number of VPCs. It's more the malignancy criteria, including this beat to beat frequency, the fastest rate. And that actually makes the holder time consuming the analysis. We look at every single VPC and look which one is the fastest. And this is not automatic. This is manual things. The key also for DCM is to do screening exams because as we said before, my toe valve is easy. Everdog has a murmur. DCM dogs may be, maybe not, probably only a soft one, if at all, to select the correct dogs for screening is very important. - Great stuff. Thank you so much, Getthard. That's a fascinating conversation and some really really important take home points. - It was a pleasure to be here with you guys. It's fun. - Thanks very much. - So thanks everybody for listening. And thank you to Dr. Vess for taking part in our podcast and talking to us about the data card I'm up to being dogs. We have got some guest lined up for the future and obviously you can stay up to date on our fourth coming episodes and release dates on our socials. So on Instagram and on Twitter, our handle is @heartbeats_pod. Thank you very much, everybody. Bye-bye. - Bye-bye. (upbeat music)